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Drugs fail in the clinic for two main reasons; the first is that they do not work and the second is that they are not safe. As such, one of the most important steps in developing a new drug is target identification and validation. A target is a broad term which can be applied to a range of biological entities which may include for example proteins, genes and RNA. A good target needs to be efficacious, safe, meet clinical and commercial needs and, above all, be ‘druggable’. A ‘druggable’ target is accessible to the putative drug molecule, be that a small molecule or larger biologicals and upon binding, elicit a biological response which may be measured both in vitro and in vivo. It is now known that certain target classes are more amenable to small molecule drug discovery, for example, G-protein-coupled receptors (GPCRs), whereas antibodies are good at blocking protein/protein interactions. Good target identification and validation enables increased confidence in the relationship between target and disease and allows us to explore whether target modulation will lead to mechanism-based side effects.