Poor adherence to medical therapy may cause as much as $100 billion in unnecessary healthcare expenses each year. Nonadherence is a complicated and dynamic problem that involves patient, medication, and prescriber factors. The Case Management Adherence Guidelines (CMAG-1) are an evidence-based algorithm that introduces concepts and strategies for assessing medical knowledge and readiness to change (motivational interviewing). Once the assessment has been made, the guidelines can be used regularly to help patients become and remain adherent to their medication regimens. CMAG-1 and its tools, based on up-to-date information about adherence and ways to promote behavioral change, are designed to identify motivational and knowledge deficiencies that may block adherence. As information accumulates from centers that use it, CMAG-1 will be modified accordingly, with the goal of creating structured interaction with patients that will increase their knowledge and motivation to take medication appropriately.