In general terms, regeneration of the musculoskeletal system requires cells, morphogens, scaffolds and an appropriate mechanical environment. Our group is trying to develop regenerative technologies that are not only scientifically sound, but also clinically expeditious and cost effective. This requires protocols that can be accomplished in a single, intra-operative procedure obviating the need for ex vivo culture of autologous cells prior to reimplantation. Of several possible approaches to achieving this, we have focused on gene delivery as a way of delivering morphogens and other such factors locally to sites of tissue damage; gene transfer can be rapid, yet expression of the transgene product may persist for a prolonged period in vivo. This strategy has been explored in conjunction with autologous marrow, skeletal muscle and fat, which are all tissues with accessible progenitor cells and scaffolding properties, those of the marrow occurring when it clots. Data exploring the use of such approaches in the healing of bone and cartilage will be described and discussed.