Purpose of review: Paraproteinemic renal diseases comprise a group of renal disorders that are difficult to manage, in part because of subtleties in the clinical presentation and confusion regarding diagnosis and appropriate therapy. Often, nephrologists make the diagnosis of the underlying plasma cell dyscrasia following renal biopsy. This review seeks to provide a greater understanding of the mechanism of disease and recent approaches to the management of patients who have AL-amyloidosis, monoclonal light-chain and light and heavy-chain deposition disease [termed ML(H)CDD], and cast nephropathy. All three renal lesions are caused by deposition of immunoglobulin light chains. This review seeks to provide a greater understanding of the mechanism of disease and recent approaches to the management of these patients. Recent findings: The immunoglobulin light chain takes the center stage in the pathogenesis of AL-amyloidosis, ML(H)CDD and cast nephropathy. Modifications in the variable domain are responsible for the affinity of the light chain for a given segment of the nephron and the subsequent toxic manifestation. Therapy aimed at eradicating the offending clone of plasma cells that secrete the monoclonal light chain chould be beneficial, but this hypothesis lacks confirmation. Four nonrandomized studies have now demonstrated clinical benefit, including return of renal function, of high-dose chemotherapy with autologous stem cell transplantation (HDT/SCT) in the treatment of patients who have AL-amyloidosis of ML(H)CDD. Summary: While randomized trials are lacking, the data support the clinical efficacy of more aggressive treatment designed to reduce the plasma cell clone responsible for these renal disorders. © 2005 Lippincott Williams & Wilkins.