Adherence to medical treatment refers to the degree to which a patient follows, or complies with, exactly the treatment prescribed by the physician. Although there is a large amount of global literature on this subject, the purpose of this chapter is to emphasize the evidence obtained in Latin America regarding adherence to medically prescribed pharmacological treatment, including a real-life regional example related to the prescription of levothyroxine. Pharmacological adherence is affected by various factors that can hinder compliance with the therapeutic regimen. This chapter systematizes five major factors, which have interdisciplinary evidence (from public health, health psychology, pharmacovigilance, among other fields): a) socioeconomic factors; b) patient-related factors; c) healthcare system-related factors; d) treatment-related factors; and e) disease-related factors. Additionally, based on the experience of the Self-Medication Behavior Observatory (Universidad del Rosario, Colombia), a special form of non-adherence is introduced, which is self-medication by altering prescribed doses. The chapter concludes with intervention alternatives to this issue and recommendations in this regard.