Multiple myeloma (MM) is caused by abnormal plasma cell growth in bone marrow, resulting in bone destruction, marrow failure, and adverse blood cell production. The course of MM is characterized by a repeating pattern of remission and relapse as patients cycle through available treatment options. Standardizing treatment options for relapsed/refractory MM poses a challenge to clinical pathway decision-makers, due to the need to individualize treatment decisions for the patient’s specific circumstances. Other challenges to treatment decision-making for relapsed/refractory MM include the disease’s heterogeneity and the proliferation of novel therapeutics and combinations. Economic consequences of the costs associated with maintenance therapy, the use of doublet and triplet regimens, and patients living longer as a result of effective treatments must also be considered. In this report, we review the complex nature of MM treatment, the current landscape of clinical practice guidelines and treatment pathways, and economic considerations for treatment.