Statins and aspirin are both widely used low-cost therapies, with known adverse effect profiles, that are prescribed to treat a symptomless condition or to prevent future adverse cardiovascular events. Despite their proven efficacy in the prevention of cardiovascular morbidity and mortality, non-adherence to these medicines is prevalent. Reported rates of non-adherence vary substantially across studies; based on meta-analyses, only every second patient who initiates statin therapy adheres to it, and non-adherence is more common in primary than in secondary prevention. Adherence to aspirin is somewhat better, being comparable to statin adherence in secondary prevention (~70%). However, these rates underestimate non-adherence by missing those who do not initiate medicine use (primary non-adherence). Use of these cardioprotective medicines is a dynamic process where adherence can change over time and many patients who discontinue medicine use reinitiate it. The most important patient-reported reason for non-adherence is adverse effects. Recently, negative media coverage has been implicated as a reason for discontinuation of statin therapy. The multitude of risk factors for non-adherence, in addition to complexity of adherence behavior, is likely to complicate efforts to improve adherence to statins and aspirin.