OBJECTIVE: To identify strategies used by a commercial managed care organization (MCO) to affect appropriate cost-effective use and prioritize payment for biologic agents. SUMMARY: With the rapid increase in the number of biologic agents and the lack of head-to-head comparative trials, determining clinical superiority of one agent may be challenging. Four case studies are presented that highlight strategies used by a commercial MCO to manage the costs and utilization of these agents and identify a preferred biologic therapy to recommend for its internally developed prior-authorization (PA) criteria for rheumatoid arthritis, asthma, psoriasis, and multiple sclerosis. The first case illustrates how the route of drug administration, differences in distribution channels, and the need for cotherapy can impact the overall cost of therapy. The second case demonstrates the need for tight control of drug utilization when a biologic agent offers only marginal incremental clinical benefit over existing options but at a substantial increase in cost. The third case provides an example of the relationship between increased efficacy and the cost of therapy, and the fourth case demonstrates that PA criteria can be flexible with respect to drug coverage when clear therapeutic differences have not been demonstrated among drugs. CONCLUSION: As more biologic agents become available, it is critical that pharmacy decision makers critically evaluate these innovative new therapies by using the best available evidence to determine the products that provide the greatest clinical and economic value.