The management of rheumatoid arthritis (RA) dramatically changed in 1998 with the introduction of etanercept and infliximab for the treatment of RA and Crohn colitis. Nine biologic agents are currently in use for treating RA. However, speculation has grown that the long-term use of these biopharmaceuticals may alter normal immunosurveillance, thereby contributing to an individual’s cancer risk. Whether malignancy is a consequence of rheumatoid inflammation or the therapies used to treat RA has been unclear until recently. This article addresses the growing data on the short- and long-term cancer risks associated with biologic use in RA.