Concern over the scale of morbidity associated with the use of oral non-steroidal anti-inflammatory drugs (NSAIDs), particularly in the elderly, has led to the development of alternative strategies for the relief of musculoskeletal and joint pain. One such is to explore the possibility of formulations that bypass the gastrointestinal tract that has proved so vulnerable to the prostaglandin inhibitory effects of NSAIDs. The success of transdermal absorption of such drugs as nicotine, oestrogens, nitrates, clonidine and hyoscine into the bloodstream has added a new dimension to drug therapy. Over the past 15 years some six topical non-steroidals (T/NSAIDs) have been licensed in the UK, and a number of others are available in other countries or are under investigation. Unlike the case with the drugs mentioned above, where the aim is to achieve a high blood level, comparable to that obtained with the oral formulation, with T/NSAIDs the desired goal is a high local concentration at the site of the lesion with, at the same time, as low a plasma concentration as possible, in order to minimise adverse GI tract or systemic effects. This paper reviews the pharmacokinetic data and the evidence for efficacy and safety, and attempts to assess the place of T/NSAIDs in current medical practice.