Multiple myeloma is frequently associated with renal dysfunction. In addition, it has been shown that the presence of renal failure indicates a higher tumor burden and consequently more aggressive disease. Patients who are diagnosed with renal insufficiency should be aggressively treated because reversal of renal insufficiency results in survival outcomes similar to patients who have normal renal function at diagnosis. However, the presence of renal impairment could add significantly to the morbidity of these patients and make it difficult to tolerate aggressive treatment regimens. Therefore, the treatment approach to this group of patients should include a thorough understanding of the feasibility and outcomes of the various antimyeloma treatments that are available, including newer options such as thalidomide. We recommend the following sequence of treatment in newly diagnosed patients with multiple myeloma with renal insufficiency (creatinine > 2 mg/dL): correction of hypercalcemia with full-dose bisphosphonates in patients with hypercalcemia, induction therapy that may be initiated before correction of hypercalcemia with bolus VAD (vincristine 2 mg, doxorubicin 40 mg/m(2), dexamethasone 40 mg on days 1-4, 9-12, and 17-20), and stem cell collection (cyclophosphamide 2.5-3 g/m(2)) with high-dose melphalan (140-150 mg/m(2)) with autologous stem cell transplant. Dialysis support should be considered whenever necessary for all newly diagnosed patients if renal function does not improve with aggressive initial therapy. For patients who develop renal insufficiency later in the course of the disease, therapeutic options need to be tailored to the patient's treatment history, disease status, and performance status.