Recent advances in oncology treatment have improved patient outcomes at the expense of increasing healthcare costs. The indication multiple myeloma is especially characterized by a recent and continuing flood of expensive novel agents. A review encompassing all elements necessary to perform an economic evaluation of novel agents for multiple myeloma was conducted for thalidomide, bortezomib and lenalidomide. Improvements in efficacy have led to a switch from conventional therapy to novel agents as standard therapy. Incremental cost-effectiveness ratios for novel agents alone or in combination with conventional agents were generally regarded to be within acceptable ranges. Conflicting results were reported for the incremental cost-effectiveness of bortezomib versus lenalidomide, as unresolved questions remain regarding their comparative effectiveness. Future economic evaluations will require an assessment of the cost-effectiveness of these agents in terms of sequence within the treatment paradigm and in combination with one another.