Multiple myeloma (MM) is a plasma B-cell malignancy that is characterized by the presence of clonal proliferation of malignant plasma cells in the bone marrow, monoclonal protein in blood or urine, and organ dysfunction. It accounts for 10% of hematological malignancies and approximately 1% of all cancers in the USA. Several etiologic agents are associated with its development. Notably, obesity is consistently associated with increased risk and drives mechanistic pathways important in its development. In addition to age, black or African American heritage is a consistent risk factor as is male gender. Epidemiologic evidence on causes and biologic pathways supporting the obesity relation are presented. Diagnosis and treatment of MM patients are considered in the context of obesity as a cause with potential impact on treatment and outcomes among those with disease.