Insurers limit the use of certain prescription drugs by requiring step therapy—that is, by allowing access only after alternatives have been tried and have failed. Using data from seventeen of the largest US commercial health plans, we examined step therapy protocols that determined patients’ eligibility for specialty drugs and identified ten diseases that are often subject to that requirement. Overall, plans applied step therapy in 38.9 percent of drug coverage policies, with varying frequency across plans (20.6–57.5 percent). Of the protocols for the ten diseases, 34.0 percent were consistent with corresponding clinical guidelines, 55.6 percent were more stringent, and 6.1 percent were less stringent. Trials of alternatives not included in the clinical guidelines were required in 4.2 percent of protocols, and the consistency of protocols varied within and across plans. These findings raise questions about potentially overly restrictive step therapy protocols, as well as concerns that variability across health plans makes protocols onerous for patients and practitioners alike. The findings thus suggest the need for state and federal legislative initiatives to help ensure appropriate prescription drug use.