The last decade has seen rapid evolution in the management of multiple myeloma. Cytogenetic, molecular, and proteomic techniques have led to a better understanding of the pathophysiology and prognostic markers of this heterogeneous malignancy. New immunomodulatory drugs, such as lenalidomide, which interrupt myeloma growth and survival pathways have entered into clinical usage. Combined with dexamethasone, oral lenalidomide has proved to be highly effective in patients whose disease has become resistant to conventional therapy. Currently, several clinical trials are ongoing in order to define the optimal use of this new agent and its combinations across the spectrum of patients with myeloma. Whether the ultimate outcome of future research will be a single-treatment solution for all patients, or whether treatments will become better-tailored to the individual (based on prognostic markers and pre-existing co-morbidities) has yet to be determined.