BACKGROUND About 50% of patients with multiple myeloma are older than 65 years and are not eligible for high-dose therapy, which has proved to be more efficacious than standard-dose chemotherapy in young patients. BACKGROUND Apart from high-dose therapy, no clear therapeutic advance has been achieved in the past 20 years, and melphalan-prednisone combinations remain reference treatments for many patients with multiple myeloma. Despite a great number of clinical trials, the use of interferon alpha is still controversial. The role of high-dose dexamethasone has been recently established and we are currently comparing dexamethasone alone, melphalan-dexamethasone and dexamethasone-interferon alpha treatments in a multicenter randomized trial (IFM 95-01). Bisphosphonates have also emerged as an efficacious and well tolerated adjuvant treatment. Optimal use of recently released bisphosphonates at various stages of the disease will possibly lead to a clear therapeutic advantage. CONCLUSIONS Other drugs, such as erythropoietin or interferon gamma require further evaluation. The recent implication of metalloproteinases in multiple myeloma and the efficacy of metalloproteinase inhibitors in animal models and phase I/II clinical studies in solid tumors provide a strong rationale for the clinical evaluation of these agents in multiple myeloma.