Multiple myeloma is characterized by monoclonal protein production, immune dysregulation, renal dysfunction and lytic bone disease. The backbone of therapy for patients eligible for high-dose therapy has been induction therapy followed by consolidation with autologous stem cell transplant. The introduction of immunomodulatory drugs and proteasome inhibitors has led to a dramatic improvement in responses to induction therapy, translating to improved survival following transplant. Despite these successes, nearly all patients will eventually relapse. The role of maintenance therapy following transplant to delay recurrence and improve survival continues to be defined. This review focuses on the most recent clinical trials for maintenance therapy, minimal residual disease detection, the risk of second primary malignancies, as well as future directions in this field.