BACKGROUND: The prognosis and treatment of multiple myeloma (MM) has evolved greatly over the past decade. The development and incorporation of new agents such as immunomodulators and proteasome inhibitors into therapy has improved outcomes and is helping patients enjoy longer periods of remission. OBJECTIVE: To review current treatments for MM, including overview of drug therapy and management of adverse effects of therapy and comorbidities. Additionally, an overview of agents being studied and evaluated for use in MM and myeloma-related conditions, such as metastatic bone disease and venous thromboembolism, will be discussed. SUMMARY: Great strides have been made regarding the understanding of disease pathology in MM, leading to therapies that may be targeted to each individual, based on their unique biology of disease. Therapy is currently tailored based on patient issues and stage of disease, but may soon be tailored individually based on the cytogenetic profile of a patient. Recent treatment guidelines have been published by the National Comprehensive Cancer Network which were updated with impressive results from clinical trials involving agents such as immunomodulators and proteasome inhibitors. This guideline also provides information on the management of myeloma and treatment-related morbidities. As with the treatment of any cancer, clinicians must weigh risk versus benefit when determining the most appropriate therapy. Currently, corticosteroids, lenalidomide, thalidomide, and bortezomib are all used in patients with MM. The use of chemotherapy, including high-dose therapy with stem cell transplant, is an important component of treatment for many patients. The use of high-dose therapy is continually being evaluated, and the issue of risk versus benefit is weighed for individual patients. Depending on the prognosis, it may be of benefit to endure the toxicity of higher doses to achieve a better overall response and achieve longer remission periods. Although stem cell transplantation is often performed in MM to improve survival and remission rates, some patients are unable to undergo transplant for a variety of reasons, including age (older than 65 years), comorbidities, and/or organ dysfunction. Newer drug therapies and combinations of therapy are being evaluated to better manage this population and patients who previously received high-dose chemotherapy and a stem-cell transplant. Additionally, the management of relapsed, or refractory, disease continues to be a challenge in treating the myeloma patient. Despite aggressive and improved treatments, most myeloma patients will eventually have resistance to therapy or relapse. Treatment strategies in these patients are also evolving. CONCLUSION: Major advancements in the diagnosis, staging, and treatment of myeloma offer promise in the future for changing MM from a terminal illness into a chronic, manageable condition.