Up to 50% of newly diagnosed plasma cell myeloma (PCM) patients can present with renal insufficiency, 20% with severe renal impairment and 10% requiring dialysis. PCM patients account for 2% of the dialysis population, adding 5000 new patients each year worldwide. Dialysis-dependent PCM patients have a 2.77 higher risk of death compared with other dialysis-dependent patients without this diagnosis. Renal failure and especially dialysis dependency is an independent poor prognostic factor in PCM, with the majority unable to achieve dialysis independence. Renal failure in PCM is a medical emergency with the need for rapid accurate diagnosis and prompt institution of supportive care and PCM-directed therapy, because reversal of renal impairment and recovery from dialysis dependency can occur in up to half the patients early in the course of disease and can lead to enormous survival benefits. Recently, the serum free light chain (SFLC) assay and serum β-2-microglobulin free heavy chain (SFHC) assay have been used to rapidly diagnose PCM in renal failure and provide prognostic information in the setting of renal failure where the Durie-Salmon and International Staging Systems do not. A renal biopsy early in the course of renal impairment can provide diagnostic and prognostic information. A new generation of dialyzers with larger pores than routine dialyzers can be used with extended hemodialysis to remove SFLC more efficiently than plasmapheresis, allowing for greater renal recovery. Novel chemotherapy agents such as bortezomib are associated with an improved renal response and have moved to the front line of therapy. Successful use of high-dose therapy and autologous hematopoietic cell transplantation (HCT) in PCM with renal failure and even dialysis dependency has been associated with late renal recovery and also allowed for the subsequent use of renal transplantation to provide even greater survival benefits. Combined non-myeloablative allogeneic HCT with renal transplant in PCM patients with end-stage renal disease on dialysis is now being studied in prospective trials.