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One of the main challenges in medicine is the lack of efficient drug therapies for common human disorders. For example, although depressed patients receive powerful antidepressants, many often remain resistant to psychopharmacotherapy. The growing recognition of complex interplay between the drug targets and the predictors of drug sensitivity requires an improved understanding of these two key aspects of drug action and their potentially shared molecular networks. Here, we apply the concept of endophenotypes and their interplay to drug action and sensitivity. Based on these analyses, we postulate that novel drugs may be developed by targeting specific molecular pathways that integrate drug targets with drug sensitivity predictors.There is a complex interplay between the drug targets (DT) and predictors of drug sensitivity (SP).This requires an improved understanding of their potentially shared molecular networks.Here, we apply the concept of endophenotypes and their interplay to DT and SP.We postulate that novel drugs may target molecular pathways that integrate DT with SP.