Patients with multiple myeloma (MM) typically respond to initial chemotherapy, but almost all patients relapse with a median survival of approximately 5 years. Combining vincristine and conventional doxorubicin with oral dexamethasone (VAD) or reduced-dose dexamethasone (VAd) provides rapid response in many patients, but its use is limited by toxicity concerns and the inconvenience of continuous infusions in each cycle. Use of pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]) and vincristine intravenous injection with oral dexamethasone (DVD) or reduced-dose dexamethasone (DVd) is safe and effective for the management of newly diagnosed or relapsed/refractory MM. Controlled trials showed that DVD/DVd is at least as effective as VAD/VAd for the treatment of MM, but DVd is associated with less neutropenia and alopecia in addition to requiring fewer days in the hospital or clinic for drug administration. DVd therapy has also been reported to be associated with an antiangiogenic effect not observed with VAD. Another liposomal anthracycline, liposomal daunorubicin (DaunoXome [DNX]), has been investigated in MM and preliminary data suggest that it is safe and effective, but studies comparing it with other regimens have not been reported. Early results from ongoing trials suggest that adding thalidomide, bortezomib, or other immune modulators to PLD-based chemotherapy may improve efficacy.