The outlook for patients with myeloma has improved dramatically over the past few years largely because of improvements in supportive care, the use of high-dose therapy, and the introduction of the novel agents thalidomide, bortezomib, and lenalidomide. These new treatment options have changed the natural history for patients with myeloma, but clinicians must consider treatment-related toxicities. Some of the most common short- and long-term toxicities include the development of peripheral neuropathy, hematologic complications, thrombosis, and bone-related complications, such as fracture and osteonecrosis of the jaw. Careful consideration of patient-reported symptoms and appropriate dose modification or prophylaxis to prevent the development of toxicity are critical, and will result in improved quality of life and better tolerance of delivered therapy.