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Multiple sclerosis is a heterogenous disease. Although several EMA-approved disease-modifying treatments including biopharmaceuticals are available, their efficacy is limited, and a certain percentage of patients are always nonresponsive. Drug efficacy monitoring is an important tool to identify these nonresponsive patients early on. Currently, detection of antidrug antibodies and quantification of biological activity are used as methods of efficacy monitoring for interferon beta and natalizumab therapies. For natalizumab and alemtuzumab treatments, drug level quantification could be an essential component of the overall disease management. Thus, utilization and development of strategies to determine treatment response are vital aspects of multiple sclerosis management given the tremendous clinical and economic promise of this tool.