This funding opportunity announcement (FOA) is being issued by the NIH Adherence Network through the Office of Behavioral and Social Sciences Research (OBSSR), with participation from multiple NIH Institutes. This FOA encourages Exploratory/Developmental Research Project Grant (R21) applications for research and development of interventions to significantly improve medication adherence in individuals. Applications may target medication adherence in the context of treatment for a single illness or chronic condition (e.g., hypertension), to stave off a disease recurrence (e.g., cancer) or for multiple comorbid conditions (e.g., hypertension, diabetes, alcohol use disorders and HIV/AIDS). A well-articulated theoretical or conceptual framework is key for applications encouraged under this announcement. Applicants should demonstrate the feasibility of collecting multi-modal data on the targets of the intervention including: a patient self-report of medication adherence, at least one non-self-report measure of medication adherence (e.g., pharmacy refill records, electronic monitoring, etc.), and a relevant health outcome or biomarker (e.g., blood pressure, viral load in HIV-infected individuals, cholesterol levels, HbA1c) that is expected to be affected by changes in the targeted adherence behavior. For diseases without identified biomarkers, inclusion of a clinical assessment (e.g., a medicine blood level, diagnostic interview or an independent clinician rating of the symptoms and behaviors) may be considered. Applications for R21 awards should describe projects distinct from those supported through the traditional R01 mechanism. For example, long-term projects, or projects designed to increase knowledge in a well-established area, will not be considered for R21 awards. Applications submitted under this mechanism should be exploratory and novel. These studies should break new ground or extend previous discoveries toward new directions or applications.