In light of increasing prevalence rates of chronic conditions and a growing elderly population, patients' nonadherence to medical regimes reflects a significant problem in modern health care. In the past, patients were primarily held responsible for problematic adherence. Over the past decades this attitude has changed dramatically, and it is now acknowledged that lack of adherence reflects a problem requiring different approaches and interventions on many different levels. Here we highlight central aspects and consequences of adherence problems in long-term therapy. Factors affecting treatment motivation in multiple sclerosis patients are summarized focusing on neurologic treatment issues, and specific intervention strategies for patients, doctors, and nurses are discussed.