Adherence to medications is poor and suboptimal in many chronic diseases. Nonadherence can reduce treatment effectiveness and can have an impact on healthcare costs. As a consequence, it may alter the cost-effectiveness of drug therapies. This article emphasizes the importance of integrating medication compliance and persistence into pharmacoeconomic evaluations, using osteoporosis as an example. A limited number of studies carried out to date have suggested important economic implications of poor adherence to osteoporosis medications. Therefore, compliance and persistence should be an integral part of clinical studies and pharmacoeconomic analyses in order to estimate the cost-effectiveness of drug therapies in current community practice. Measuring adherence and incorporating it into health economic modeling may, however, pose particular challenges.