AL amyloidosis is the most common form of systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. It is often difficult to recognize because of its many manifestations. Recent diagnostic and prognostic advances include the serum-free light chain assay, cardiac MRI, and serologic cardiac biomarkers. Treatment strategies that have evolved during the past decade are prolonging survival and preserving organ function. This article outlines the role of high-dose melphalan and stem cell transplantation. This year marks the 20th anniversary for the first patient who underwent successful stem cell transplantation for this disease at Boston Medical Center.