Multiple myeloma is an incurable disease for which there are 2 clinical research strategies. One strategy is to focus on managing the disease as a chronic process aiming to minimize the negative impact on survival with minimal or no compromise of the quality of life. The other strategy is to pursue total eradication of the malignant clone, thus achieving cure for the disease. Over the past decade, the myeloma communities have seen several new agents approved for the therapy of multiple myeloma. Although these agents do not result in cure, they target the disease microenvironment, allowing for a better overall response rate and improved quality of response. The latter appears to be influencing the disease outcome in improved progression-free survival, translating into a longer overall survival. Despite the advances in the discovery of immune modulator compounds, chemotherapy continues to be an important part of the myeloma therapeutic armamentarium. Recently, several investigators have explored combining traditional chemotherapeutic agents with proteasome inhibitors and immune modulators.