Noncompliance or nonadherence with medical regimens represents a major challenge to the practice of medicine including the treatment of headache. Indeed, medication use patterns are particularly relevant to headache because of the potential for headache therapies to induce medication-overuse headache. Previous research has demonstrated that adherence to long-term medication therapy for various chronic illnesses averages only about 50%. The rate of adherence among headache patients has been found to be similarly poor. Misuse or overuse of symptomatic medication has been demonstrated to contribute to treatment failure, and one-fourth to one-half of patients are noncompliant with prophylactic headache medications and at least 40% nonadherent with appointment-keeping. Adherence declines with more frequent and complex dosing regimens, side effects, and costs, and is subject to a wide range of psychosocial influences. Subjective reports of adherence are likely not only to overestimate but also to be discordant with more objective measurements. As the first of 2 articles, this paper describes the problem of noncompliance in medical practice and reviews literature addressing compliance specific to headache management. A companion paper (Behavioral Facilitation of Medical Treatment for Headache—Part II: Theoretical Models and Behavioral Strategies for Improving Adherence) summarizes social learning models proposed to characterize the multiple determinants of adherence and guide behavioral adherence-enhancing interventions, and then presents cognitive and behavioral strategies that may facilitate treatment adherence with headache patients.