OBJECTIVES: We define 'compliance' as the 'the extent of correspondence between the patient's dosing history and the prescribed dosing regimen', and 'persistence' as the time between the first- and last-taken doses. They are related in that persistence increases one dose at a time. Shortfalls in both have differing economic consequences. The frequency distribution of drug intake is remarkably similar across disparate diseases and drugs, though poor methods and terminology have led many to believe otherwise. METHODS: Figure 1 shows that similarity in 275 patients electronically monitored for 1-12 months, receiving pharmacotherapy for glaucoma, epilepsy, or ankylosing spondylitis. We transformed these data into a frequency distribution of time-to-consume a 60-day supply of drug, which ranged from 60-422 days, with a median of 71 and a mean of 78 days, i.e., a mean of 4.7 refills/year instead of the prescribed 6 - a 22% shortfall in refills and revenues. RESULTS: We projected the impact of variable persistence using a model expressing patients' movements between: treated, never treated, formerly treated, dead or otherwise untreatable. We used published data on statin persistence to analyze various scenarios. With fixed monthly recruitment of patients into treatment, the divergence in revenues from the 'perfect persistence' scenario is projected to result at the 15 year point in an ~80% shortfall in annual revenues. CONCLUSIONS: Published data may underestimate generally prevailing persistence, which would lessen the shortfall in revenues, but the impact on profits appears to be strikingly high. Methods that efficiently extend persistence are needed for the benefit of all parties.