Although not often openly acknowledged, “cure versus control” is the dominant philosophical difference behind many of the strategies, trials, and debates related to the management of myeloma. Should we treat patients with myeloma with multidrug, multitransplant combinations with the goal of potentially curing a subset of patients, recognizing that the risk of adverse events and effect on quality of life will be substantial? Or should we address myeloma as a chronic incurable condition with the goal of disease control, using the least toxic regimens, emphasizing a balance between efficacy and quality of life, and reserving more aggressive therapy for later? To be sure, if cure were known to be possible (with a reasonable probability) in myeloma, it would undoubtedly be the preferred therapeutic goal of most patients and physicians. But this is not the case. Myeloma is generally not considered a curable disease; however, new definitions of cure have been suggested, including operational cure, which is defined as a sustained complete response (CR) for a prolonged period. (1,2) Cure versus control is debated because the strategies currently being tested are not truly curative but rather are intended to maximize response rates in the hope that they will translate into an operational cure for a subset of patients. For decades, the treatment of myeloma was restricted to conventional chemotherapy with alkylators and corticosteroids, and the question of cure versus control never arose. The response rate with alkylators and corticosteroids was only about 50%, and CR (3,4) was rare. Cure was never a goal of therapy because it was assumed to be unattainable. Instead, the goal was to control the disease as much as possible, providing the best quality of life to the patient for the longest duration by judicious, intermittent use of the 2 available classes of active chemotherapeutic agents. In the 1990s, high-dose therapy with autologous stem cell transplant (ASCT) became part of standard practice when it was found to prolong survival compared with conventional chemotherapy. (5-7) Subsequently, bisphosphonates were found to be effective in decreasing the incidence of bone lesions. (8,9) In the past decade, thalidomide, (10) bortezomib (11-13) and lenalidomide (14,15) emerged as effective agents for the treatment of myeloma, producing spectacular results in combination with other known agents in terms of response rate, CR rate, progression-free survival (PFS), and (more recently) overall survival. Numerous combinations have been developed, resulting in a veritable alphabet soup of clinical trials (16) and drug combinations are vying with each other for the highest response rate (and prominence). (17,18) The results obtained with new combinations have indeed been remarkable and have prompted a relatively new philosophy of treating myeloma with the goal of potential cure rather than disease control. These philosophical differences underpin the various clinically relevant debates regarding myeloma currently confronting patients and