Outcomes for patients with multiple myeloma have dramatically improved during the past 20 years as a result of improved therapeutic options and a better understanding of malignant plasma cell biology. Until the past 10 years, the major limitations on improving outcomes were related to the minimal efficacy of existing agents and balancing the toxicity of therapy in an older patient population. However, despite these limitations, there have been advances that have resulted in improvements in progression-free survival and overall survival (OS). High-dose therapy and autologous transplant were the first among therapies to demonstrate an improvement in OS; but more recent analyses have demonstrated that there can be improvement in OS, which is also associated with improvement in the complete response (CR) rate, even among nontransplant patients as well. Thus, achieving CR has been associated with improved OS and has become a therapeutic goal. In the current era of new agents, such as thalidomide, bortezomib, and lenalidomide, the fraction of patients who achieve a CR is now greater than before, and the data regarding the importance of achieving this benchmark of response have never been more benefit.