SUMMARY There have been many advances in the treatment of patients with multiple myeloma over the past decade. As a result, the average life expectancy of patients with MM has improved. New medications, including immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide) and proteasome inhibitors (bortezomib and carfilzomib) have entered clinical practice. On average, these medications are easier to tolerate than traditional chemotherapy allowing for long-term use of these drugs in a maintenance fashion. Clinical trials have appeared to establish the benefit of lower dose maintenance therapy for MM patients after induction chemotherapy and/or autologous stem cell transplant. These medications have been shown to improve not only the progression-free survival of patients, but also improve their overall survival compared with observation alone in some pivotal studies. With long-term maintenance therapy, a notable increase in secondary primary malignancies has been described. The exact mechanism behind this increase is uncertain, but may relate to the persistence of CD34+ cells in the setting of continued immunomodulatory exposure. Despite the concern of secondary primary malignancies, the risk:benefit ratio still favors maintenance therapy in many patients with multiple myeloma.