Primary systemic amyloidosis is an immunoglobulin light chain disorder that is 1/5th as common as multiple myeloma. Amyloidosis is regularly seen in the practice of a hematologist and has recently undergone major advances in terms of the ability to evaluate responses as well as new therapeutic options that were not available when this topic was covered as an education session at the American Society of Hematology meeting 5 years ago. Waldenström macroglobulinemia (WM) is rarer than amyloidosis (1500 per year WM versus 3000 per year amyloid in the US), and recent consensus panels have established the definition of the disease, the diagnostic criteria, criteria for initiation of therapy and a new classification scheme. In this session, new developments in amyloid and macroglobulinemia, from suspicion of the diagnosis to treatment, are covered. In Section I, Dr. Morie Gertz answers four specific questions: (1) When should amyloidosis be suspected? (2) How does one heighten ones index of suspicion for amyloid? (3) How is the diagnosis confirmed and the type classified as primary? (4) What is the prognosis and how is it accurately assessed? Recent findings on cardiac biomarkers, presenting features and use of the free light chain assay are reviewed. Staging for amyloid and recently proposed criteria of response and progression are covered. In Section II, Dr. Giampaolo Merlini comprehensively reviews therapy of amyloidosis from the use of standard melphalan/prednisone to the recently described standard dose therapies including dexamethasone, thalidomide/dexamethasone, melphalan/dexamethasone and IV melphalan/dexamethasone. An extensive discussion of the role of high-dose therapy with stem cell reconstitution follows and includes patient selection, predictors of immediate morbidity and mortality, and survival expectation. Finally, a therapeutic strategy is proposed. In Section III, Drs. Steven Treon and Giampaolo Merlini review the most current information on WM. The consensus panel results and recommendations of the clinical pathologic definition of WM, the prognostic markers and the indications to initiate therapy in WM, the uniform response criteria in WM and available treatments for the disease are reviewed. Drs. Treon and Merlini cover recently published treatment protocols that use rituximab, purine nucleoside analogs, and alkylating agents. The current data on thalidomide, alpha interferon, and high-dose therapy are also covered.