Multiple myeloma (MM) is characterized by the presence of osteolytic bone disease, renal impairment, anemia, and immune dysfunction. Adequate supportive care is considered an essential part of anti-myeloma therapy. The administration of bisphosphonates has been shown to reduce skeletal related events and hypercalcemia. Bisphosphonates are well tolerated, but preventive steps should be taken to avoid renal impairment and osteonecrosis of the jaw (ONJ). Adequate pain control is of crucial importance for the quality of life of MM patients. Local radiotherapy may rapidly ameliorate symptoms of painful MM bone lesions, and vertebroplasty and kyphoplasty are able to control symptoms and restore the original height of vertebral fractures. Symptomatic chemotherapy-induced anemia should preferentially be treated with erythropoietic growth factors, but further studies are required to confirm the long-term safety of this approach. Light-chain-induced renal impairment should be treated without delay with a highly effective anti-myeloma regimen consisting of novel drugs. Prophylaxis of infections should be considered particularly in patients with poorly controlled disease and documented infections should be treated aggressively as they contribute significantly to morbidity and mortality. The concerted action of these supportive therapies can significantly improve the quality of life of MM patients during the different phases of their disease.