Interventions to improve medication adherence have had limited success and can require significant human resources to implement. Research focused on improving medication adherence has undergone a paradigm shift, of late, with a shift towards developing personalized, theory-driven interventions. The current research integrates foundational and translational science to implement a mechanisms-focused, context-aware approach. Increasing adoption of mobile and wearable sensing systems presents new opportunities for understanding how medication-taking behaviors unfold in natural settings, especially in populations who have difficulty adhering to medications. When combined with survey and ecological momentary assessment data, these mobile and wearable sensing systems can directly capture the context of medication adherence in situ, including personal, behavioral, and environmental factors. The purpose of this paper is to present a new transdisciplinary research framework in medication adherence, highlight critical advances in this rapidly-evolving research field, and outline potential future directions for both research and clinical applications.