Multiple myeloma, a hematologic malignancy of plasma cells characterized by excessive monoclonal protein production, accounts for 36,000 new cancer diagnoses annually in the United States. The median age at diagnosis is 69 years. Multiple myeloma may present with symptoms, such as bone pain, fatigue, anemia, weight loss, kidney failure, and hypercalcemia, although some patients are asymptomatic. Initial evaluation includes complete blood cell count, comprehensive metabolic panel, serum calcium level, urinalysis, thyroid-stimulating hormone (thyrotropin), urine and serum protein electrophoresis, and radiography of symptomatic bony sites. Diagnosis relies on a combination of urine and serum protein electrophoresis, serum immunofixation, serum free light chain assay, imaging (computed tomography or positron emission tomography-computed tomography), and bone marrow analysis. Oncology referral is recommended if the initial evaluation is suggestive of multiple myeloma. Treatment is determined by a combination of disease characteristics and patient factors and typically involves a three- to four-drug regimen followed by autologous stem cell transplantation if eligible, and then maintenance therapy. Adjunctive care includes bisphosphonates or denosumab and venous thromboembolism prophylaxis. Family physicians play a crucial role in the patient's multidisciplinary team for addressing psychosocial needs, identifying relapse or recurrence, and managing comorbidities.