Poor adherence to treatment regimens has long been recognized as a substantial roadblock to achieving better outcomes for patients. Non-adherence to medications affects the quality and length of life and has been associated with negative health outcomes and increasing healthcare costs. The problem of non-adherence is particularly troublesome in older patients who are affected by multiple chronic diseases and for this reason receive multiple treatments. To date, no single intervention strategy has been shown to be effective in improving adherence across all patients, conditions, and settings. Between September and October 2014, a group of experts in geriatrics, pharmacology, epidemiology, and public health applied a modified RAND appropriateness method to reach a consensus on the possible best interventions to improve adherence in older individuals. Seven interventions were identified, classified based on their target (patient, therapy, and public health/society): (1) Comprehensive Geriatric Assessment, (2) patient (and caregiver) education to improve patient empowerment, (3) optimization of treatment, (4) use of adherence aids, (5) physician and other healthcare professionals' education, (6) adherence assessment, (7) facilitating access to medicine by service integration. For each intervention, experts assessed (a) target population, (b) health professionals potentially involved in the intervention, (c) strategies/instruments needed for implementation, and (d) time of the intervention. Interventions that target adherence must combine different approaches targeting the complex aspects of older adults in a holistic approach. Tackling non-adherence, with its complexity, requires a multi-stakeholder patient-centred approach acting in a defined framework of interactions in which the different players may provide different services but are integrated with one another.