Dose-intensive therapy with hematopoietic cell transplantation is effective at reversing AL amyloidosis but is not without risk. Guidelines have been developed for patient selection in order to maximize benefit and minimize treatment-related mortality. Identification of a patient's clonal germline light chain variable region gene may become relevant to patient selection, and development of less morbid approaches to stem cell mobilization and collection would be helpful. While there is room for discussion regarding the design of future therapeutic trials, it is reasonable to attempt to improve the complete response rate for good risk patients by continuing efforts on the phase II level. Attempts to improve outcomes for patients with symptomatic cardiac or advanced multisystem disease may require serial solid organ and stem cell transplantation as well as the development of less toxic approaches using lower doses of melphalan, improved supportive care measures and specific organ-system prophylaxis. If outcomes can be improved, issues related to clonotypic contamination of stem cells will need to be revisited.