Drugs that modulate the renin-angiotensin-aldosterone system (RAAS) play an important role in modern cardiovascular prevention strategies. Inhibitors of the RAAS, in particular angiotensin-converting enzyme (ACE) inhibitors, have been proven to be beneficial in specific patient groups, including patients with hypertension, heart failure, diabetes mellitus and stable coronary artery disease. Although clinical trials demonstrated a rather consistent beneficial effect of ACE inhibitors across groups of patients based on clinical characteristics, the variability in treatment response on the individual patient level is extensive. Recent publications suggest that genetic polymorphisms in the RAAS are related to cardiovascular risk. Genetic variability also seems associated with the response to ACE inhibitor therapy, and can probably be used to tailor treatment. This review discusses several approaches to guide ACE inhibitor therapy in patients with coronary artery disease. In addition, the potential impact of pharmacogenetics regarding this particular topic is highlighted.