Pharmacology is, by definition, the study of the mechanism of action of drugs, and requires a knowledge and understanding of responses to drugs induced both in vitro and in vivo. Such analysis of drug action is needed to transform molecular or cellular discoveries into clinical practice and, equally, to identify the molecular questions that arise from clinical observations. These studies are essential because responses observed in vitro can be magnified, diminished or totally different in the more complex integrated system. However, there is currently a severe shortage of pharmacologists with the skills needed to carry out in vivo studies in medical research, and a diminishing number of academic staff qualified to teach these skills to students. This article explores the reasons for this situation and outlines why in vivo work is vital for the analysis of drug action and for the discovery and development of new therapeutic agents.