AL amyloidosis is the only form of amyloidosis caused by a small plasma cell clone in the bone marrow. The produced aberrant free light chain forms, together with serum amyloid P, deposits in several organs leading to organ dysfunction. Involvement of the heart is the most important prognostic factor. Treatment of systemic AL amyloidosis is based on treatments as used in multiple myeloma, however is much more complicated due to organ dysfunction and worse clinical condition of the patients. Aim of treatment is to achieve a complete haematological response. Organ responses can occur later on. High dose melphalan followed by stem cell transplantation is given to younger en fit patients. Older patients are treated with oral melphalan and dexamethasone. Bortezomib also seems to be well tolerated by patients and has good clinical efficacy. Several randomised phase III studies, such as the HOVON 104, have started to investigate superiority of treatment with proteasome inhibitors. Treatment of patients in clinical studies is highly recommended.