The first successful gene therapy trial was reported in 1991. Since then, successful gene transfer in cultured cells and small animals has been reported by many studies, with achievement of at least transitory high levels of exogenous gene expression. Over 400 clinical protocols for gene therapy have been approved, involving over 4000 patients. However, publication of the results of these gene therapy trials has been limited, with only 80 published reports as of 2002. The majority of clinical gene therapy trials reported so far have been phase I or phase II trials, which are concerned mainly with safety issues and have focused on the treatment of malignancies and other potentially fatal conditions. The death of a patient in 1999 from systemic administration of an adenoviral vector and recent reports of leukaemia in two patients in a clinical gene therapy trial have led to a further re-evaluation of the safety of gene therapy and the role for gene therapy in clinical practice. This review outlines the current status of gene therapy as it relates to orthopaedic diseases and highlights the areas where progress is still to be made.