Treatment of multiple myeloma (MM) remains highly individualized, with multiple factors that play a role in determining the best course of therapy. Patient-specific criteria such as age of onset, whether the patient is symptomatic at the time of diagnosis, and any detected high-risk cytogenic abnormalities are all considerations when selecting a regimen. Newer agents such as bortezomib and lenalidomide in combination with low-dose steroids have replaced more toxic chemotherapeutic regimens for primary induction and have led to significant increases in progression-free survival. Depending on duration of response prior to relapse, patients may be rechallenged with the same regimen, switched to an alternative, or may undergo hematopoietic cell transplant (HCT), which remains a highly effective treatment option for patients who are candidates. However, the cost of transplantation remains high and some patients may require a second transplantation if the initial response is incomplete. With the availability of newer agents for salvage therapies in refractory or relapsed patients, the reliance on HCT may decrease, potentially lowering healthcare costs. In addition, the availability of orally active agents may decrease the need for outpatient infusions, thus decreasing the overall costs associated with treatment and improving patient satisfaction. Finally, combination regimens that use lower doses may prove to be less toxic as well as more effective. Even though MM only accounts for approximately 1% of all cancers in the United States, with 75 million “baby boomers” now reaching the median age of diagnosis, the increased number of cases could have a substantial impact on healthcare costs.