Several different myeloma gene therapy approaches are currently being explored, seeking to impact on the disease process in diverse ways. Therapeutic benefit may result from destroying the myeloma cells directly, provoking an antimyeloma cell immune response, interfering with the paracrine growth signaling pathways between osteoclasts and myeloma cells, or genetically manipulating hematopoietic progenitors or mature T cells in a stem cell transplantation setting. Encouraging progress in each of these areas is being fueled by the development of improved viral and nonviral gene transfer vectors.