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Prescribing medical therapy for the treatment of glaucoma can be a complex process since many parameters should be taken into consideration regarding its achievements and limits. Today, a variety of options, including multiple drug classes and multiple agents within classes, are available to the clinician, but caution should be given to their side effects and contraindications. Glaucoma patients with preexisting ocular surface disease should be treated with caution, and preferably with preservative-free formulations, as there is an increased risk for symptom deterioration. The development and use of fixed-combination therapies has reduced the preservative-related side effects that threaten patient adherence and has minimized the washout effect of multiple instillations. Adherence to medical treatment is not only crucial to its efficacy but also to its cost-effectiveness. Further factors to consider are that there are patients who are nonresponders to treatment, and also that the target intraocular pressure (IOP) cannot be reached in all patients, regardless of the response to treatment. The progression of damage can occur even under maximum medical treatment or maximally tolerated medical treatment, and regardless of whether low IOP levels are reached. Furthermore, there is some conflict between medical treatment and quality of life due to long-term everyday use and to side effects of treatment. New molecules and new delivery systems are being investigated to open new horizons in glaucoma management. Although the general rule is to initiate glaucoma management with medical treatment, the limits of medical therapy should be considered to identify those patients in need of surgical management., (© 2017 S. Karger AG, Basel.)