Gene therapy offers great possibilities for treating rheumatoid arthritis (RA). Traditional surgical and pharmaceutical methods of treating RA have met with limited therapeutic success and have failed to produce a cure, but the past several years have seen extensive progress toward development of a gene therapy for arthritis. Numerous vectors and therapeutic genes have been investigated in animal models of arthritis, and the potential of gene therapy to treat or manage RA has been demonstrated in several clinical studies. Gene therapy offers the possibility of overcoming many of the limitations of current biologic therapies by providing long-term, high-level localized expression of therapeutic genes, potentially in as little as a single dose. In this review, we explore the advances in gene therapy for RA and summarize the recent preclinical and clinical data. In addition, we provide an overview of vectors and targets for RA gene therapy.