Multiple myeloma (MM) is an incurable plasma cell dyscrasia that remains fatal. Despite efforts over the past 3 to 4 decades, the median survival of patients with MM does not exceed 3 to 4 years. Although patients receiving combination chemotherapy have higher response rates compared with those receiving oral melphalan and prednisolone, they have no survival advantage. High-dose chemotherapy followed by autologous stem cell transplantation has documented benefit over conventional treatment and is currently the accepted mode of treatment for symptomatic MM. Allogeneic transplantation is associated with high complete remission rates, but at the cost of high therapy-related mortality. Maintenance treatment with interferon-alpha shows benefit, albeit in a small fraction of MM patients. The use of bisphosphonates in patients with MM has clearly demonstrated benefit and reduced morbidity associated with bone disease. All of these measures have improved remission rates and survival, but all patients with MM ultimately relapse and succumb to their disease. Novel therapeutic strategies are therefore required to improve outcome of MM patients. The responses noted to thalidomide in MM are encouraging. Immune-based strategies, including both adoptive immunotherapy and vaccinations, are currently being investigated in the preclinical and clinical setting, with the goal of enhancing autologous and allogeneic anti-MM immunity for therapeutic applications.