A key factor to successful secondary prevention of cardiovascular disease (CVD) is optimal patient adherence to treatment. However, unsatisfactory rates of adherence to treatment for CVD risk factors and CVD have been observed consistently over the last few decades. Hence, achieving optimal adherence to lifestyle measures and guideline-directed medical therapy in secondary prevention and rehabilitation is a great challenge to many healthcare professionals. Therefore, in this European Association of Preventive Cardiology clinical consensus document, a modern reappraisal of the adherence to optimal treatment is provided, together with simple, practical, and feasible suggestions to achieve this goal in the clinical setting, focusing on evidence-based concepts.