Multiple myeloma (MM) is a neoplastic proliferation of plasma cells within the bone marrow. The disease is characterized by a plasma cell infiltrate of the bone marrow, osteolytic bone lesions, and the presence of monoclonal protein in the serum or urine with extraosseous involvement by disease less common. Although the skeletal survey has long been the standard investigation in these patients, there have been significant recent advances in computed tomography (CT), magnetic resonance imaging (MRI), and functional imaging. We present a comprehensive review of the evidence for the use of each of these studies in the diagnosis, prognosis, assessment of complications, and response evaluation in patients with MM.