For people living with a long-term condition, optimal use of prescribed medications in line with evidence-based guidelines is necessary to achieve the best possible therapeutic effect and health outcomes. However, many people do not take their medicines as prescribed. Despite decades of research, medication nonadherence continues to be a challenge to global health, contributing to increased morbidity, mortality and healthcare costs. Adherence interventions have had limited success, with the most effective interventions typically being too complex to implement in practice in a sustainable way. There is a need for a more simple and pragmatic intervention approach. This chapter outlines the predominant approach and health psychology theory that underpins explanations of nonadherence and the development of effective interventions. The Perceptions and Practicalities Approach can be used to conceptualize the minimum effective ingredients of adherence support targeted at the level of the individual to address motivation and ability. Patients’ beliefs about treatment are pivotal and can be operationalized using the Necessity-Concerns Framework. This can also be used to extend Leventhal’s Common-Sense Self-Regulatory model to specify the key perceptions underpinning the motivation to start and continue with medical treatments.