In the past decade, the introduction of bortezomib, thalidomide, and lenalidomide has changed the treatment of multiple myeloma (MM) dramatically. Combinations of bortezomib or lenalidomide with dexamethasone have improved response rates and prolonged response duration compared with older approaches. However, many patients will relapse, and efforts to improve survival are still needed. Several clinical studies have demonstrated that bortezomib- or lenalidomide-based triplet regimens have improved activity compared with doublet regimens. Bortezomib and lenalidomide have different but overlapping mechanisms of anti-MM activity in preclinical studies. In several studies, the triplet regimens of lenalidomide, bortezomib, and dexamethasone (RVD) have shown significant efficacy and favorable tolerability in both newly diagnosed and relapsed/refractory multiple myeloma. In this review, we will focus on RVD therapy for myeloma treatment.