L-PAM and prednisone (MP) has been challenged, almost from the start, by combination chemotherapy (CT) with its strong theoretic backing, as the standard chemotherapy for multiple myeloma. In effect, the two contestants were really evenly matched. Unfortunately, neither of them has been able to provide a satisfactory weapon against this remarkably resistant disease. This lack of an effective therapy has stimulated both the search for new strategies and an ongoing controversy. MP remains the standard induction chemotherapy for MM. Nevertheless, in several clinical conditions CT is preferable. The 18% of MM patients who show at presentation acute or chronic renal failure may be safely treated with regimens including cytotoxic drugs with a nonrenal excretion, such as doxorubin. Moreover, low-dose oral melphalan is not recommended for young patients in the event of their enrollment in high-dose programs. The standard chemotherapy for MM will continue to be an area of great controversy until a new treatment strategy proves to be clearly superior in large randomized studies.