When an aptly prescribed medicine has not worked as expected, the potential explanations logically fall among three categories: pharmacodynamic, pharmacokinetic, and pharmionic. Pharmacodynamic reasons include problems in drug reception created by deficient or absent receptors, when disease or comorbidities are too severe for the agent’s usual therapeutic benefits to express themselves, when unusually strong physiological counter-regulatory actions attenuate or nullify the drug’s usual actions, and others – obviously a whole topic in its own right. Pharmacokinetic reasons include problems with drug absorption or unusually high rates of presystemic or systemic drug metabolism, or of other clearance mechanisms, resulting in unusually low concentrations of drug in plasma and other body fluids arising from the usually satisfactory, recommended dosage regimen. Pharmionic reasons include failure of the medicine to be taken in the doses, at the times, and in keeping with other dosing instructions that are needed, ceteris paribus, for satisfactory therapeutic action. Pharmionic? ‘Pharmionic’ is the adjectival form of the name of a nascent discipline, pharmionics, which is concerned with factors that measure and control the use of prescription pharmaceuticals. The suffix ‘ionic’ comes from the Greek verb ‘to go’ [1]. Pharmionics is akin to ‘avionics’, which is the discipline and technologies concerned with the measuring and controlling of flight in aircraft – ‘the going’ of the airplane. Avionics began and grew in importance as advances in aircraft pushed speed and acceleration past the point that pilots could safely rely on direct vision, a compass, an altimeter, and ‘seat of the pants’ sensations for controlling flight. Today’s means of measurement, communication, and control have superseded the simple approaches that can suffice when flight is slow, low, and in ideal weather. Analogously, one can reasonably say that pharmacotherapeutics has reached or passed the point where the power and complexity of medicines require formalization into disciplinary terms of the methods of measurement, communication, and control needed to improve the likelihood, if not assure, that powerful medicines are administered in appropriate doses, at appropriate times, under appropriate circumstances. These are the topics that comprise the subject matter of pharmionics. The etymology of ‘pharmionics’ indicates its basic concern with ‘the going of the prescription drug – ‘going’ in the sense that a manufactured dosage form must, if it is to play its therapeutic role, travel from the package in which it is dispensed by a pharmacy into the patient’s mouth, and down the oesophagus to the stomach. At that point, the discipline of pharmacokinetics takes centre-stage, dealing with subsequent conversion of drug into metabolites and movement into the bloodstream, toward receptors or other sites of action, which fall under the discipline of pharmacodynamics. The distances that the drug travels under the purview of pharmionics are a few metres more than the meter or so that drug travels under the purview of pharmacokinetics. One can envision a further spatial compression from metres to the angstroms involved in the receptor docking/undocking that could reasonably be considered the domain of pharmacodynamics, beyond which receptor-generated message(s), but usually not the drug molecules themselves, may travel locally or in some cases systemically. Undocked drug molecules return to the domain of pharmacokinetics, for metabolism and/or excretion. In terms of what can go wrong in ambulatory pharmacotherapy, history shows that things can go wrong at every point along the medicine’s travels from pharmaceutical factory to drug receptor. Most errors occur, however, after the dispensing of the prescription, when the patient becomes responsible for the penultimate steps in the whole chain from factory to receptor. Errors made at any point in, or segment of, those travels can nullify or otherwise pervert therapeutic intentions of manufacturers, prescribers, and pharmacists. This view was nicely codified by Carl Peck and the late John Harter in a valuable paper in 1991 [2], recently fine-tuned [3]. But given that errors at any point can nullify, thwart, or confound therapeutic intent, it might seem odd to a visitor from outside the pharmaceutical-medical world that attention is so markedly focused on just the pharmacokinetic phase of the overall process. This imbalance reflects probably several factors. One, of course, has been the phenomenal advances in analytical chemical methods during the past 3 decades, which have greatly facilitated studies of the disposition of ingested or otherwise administered drug within the body – ‘what the body does to the drug’. In contrast, pharmacodynamics – ‘what the drug does to the body’ – has been vexed by the methodologic difficulties of reliably quantifying the manifold types of drug action, many of which cannot be expressed in the numerical terms that most scientists have been trained to seek, but which must instead be quantified in clinimetric terms that relatively few scientists have been educated to develop and apply to clinically pressing problems. Against the foregoing two backdrops, the nascent discipline of pharmionics could hardly begin to be contemplated until the integration of time-stamping microcircuitry into pharmaceutical packages made it possible to compile reliable data on ambulatory patients’ dosing histories [4–7]. That development, which by now has compiled an extensive range of published applications [8], represents the ‘technological push’ side of the story, as important to pharmionics as the advances in analytical chemistry since 1960 have been to pharmacokinetics. The medical need, or ‘pull’ for pharmionics, arises from the increasing power and specificity of drug actions, reflected by the increasing use of patients’ responses to certain prescribed drugs as bases for medical decision-making. This aspect of medical practice is exemplified by, but certainly not limited to, the ‘stepped-care’ approach to treating arterial hypertension [9]. Stepped-care management includes the concept of first-, second-, and third-line agents. In general, a patient’s failure to respond to treatment with a first-line agent is an indication to escalate the strength of the prescribed treatment. Escalation can variously be done by raising the dose of the already-prescribed agent(s), by adding a further first-line agent, by combining a first- and second-line agent, or by switching completely to a second-line agent. Persistent nonresponse is interpreted as an indication to proceed toward so-called ‘triple therapy’, i.e. three concomitantly prescribed drugs drawn mainly from 2nd and 3rd line agents. Similar ideas that nonresponse should drive progression through 1st, 2nd, and 3rd line agents toward a 3-drug ‘ultimate’ regimen is found in epilepsy, glaucoma, and other chronic diseases for which numerous choices of drug are available. Lip-service is, of course, given to the possibility that nonresponse may be consequent to poor compliance, but that sensible advice is nullified by the fact that, in the absence of electronic monitoring, the clinical ascertainment of patient compliance is aptly described as no better than a coin-toss [10].