Multiple myeloma accounts for 1.6% of all cancer cases and approximately 10% of hematologic malignancies in the United States. In 2015, an estimated 28,850 new cases of multiple myeloma were diagnosed in the United States, and the disease caused more than 11,000 deaths. Patients older than 65 years account for 85% of those diagnosed with multiple myeloma, and there is a twofold increased incidence in blacks compared with whites. Patients may present with bone pain or with symptoms that are often nonspecific, such as nausea, vomiting, malaise, weakness, recurrent infections, and weight loss. Many patients present with only laboratory abnormalities, such as anemia, renal disease, and elevated protein levels. The diagnosis of multiple myeloma requires increased numbers of immature, abnormal, or atypical plasma cells in the bone marrow; a monoclonal protein in the serum or urine; or characteristic bone lesions. The diagnostic workup in a patient with suspected multiple myeloma should include a complete blood count with differential; serum chemistries; creatinine, lactate dehydrogenase, and beta2-microglobulin tests; immunoglobulin studies; skeletal survey; and bone marrow evaluation. Initiation of chemotherapy and assessment of eligibility for autologous stem cell transplantation require referral to an oncologist. Most patients with multiple myeloma will receive thromboprophylaxis, bisphosphonate therapy, and prophylaxis against infection at some point in their treatment. Family physicians play a role in assessing these patients for infection, adverse treatment effects, and renal and thrombotic complications, and in managing issues related to pain, nutrition, and psychosocial support.