Therapeutic advances in the treatment of multiple myeloma have significantly improved remission duration and overall survival (OS). These strategies have included the use of immunotherapy (interferon), novel agents (bortezomib, thalidomide, and lenalidomide), corticosteroids, and chemotherapy. While novel agents have had a major impact on response rates with initial therapy, most patients with multiple myeloma will eventually relapse. In the setting of minimal residual disease following standard dose or high-dose therapy, a number of different 'maintenance' strategies have emerged to prolong the duration of initial or subsequent remissions. The impact of these strategies on OS and event-free survival (EFS) is critically important, as the use of ineffective maintenance therapy adds the burden of additional cost, morbidity, and may reduce quality of life. Truly successful maintenance therapy will be effective in the setting of minimal residual disease, and will improve not only EFS, but also OS. This review summarizes the currently available data in the maintenance setting for multiple myeloma, and will discuss potential future trials to further address this important issue.