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SummarySeveral recent developments are brought together: (i) the new availability of a consensus, curated human metabolic network reconstruction (Recon2), approximately a third of whose steps are represented by transporters, (ii) the recognition that most successful (marketed) drugs, as well as natural products, bear significant similarities to the metabolites in Recon2, (iii) the recognition that to get into and out of cells such drugs hitchhike on the transporters that are part of normal intermediary metabolism, and the consequent recognition that for intact biomembrane Phospholipid Bilayer diffusion Is Negligible (PBIN), and (iv) the consequent recognition that we need to exploit this and to use more phenotypic assays to understand how drugs affect cells and organisms. I show in particular that lipophilicity is a very poor predictor of drug permeability, and that we need to (and can) bring together our knowledge of both pharmacology and systems biology modelling into a new systems pharmacology.