Adverse drug reactions (ADRs) occur frequently in modern medical practice, increasing morbidity and mortality and inflating the cost of care. Patients with cardiovascular disease are particularly vulnerable to ADRs due to their advanced age, polypharmacy, and the influence of heart disease on drug metabolism. The ADR potential for a particular cardiovascular drug varies with the individual, the disease being treated, and the extent of exposure to other drugs. Knowledge of this complex interplay between patient, drug, and disease is a critical component of safe and effective cardiovascular disease management. The majority of significant ADRs involving cardiovascular drugs are predictable and therefore preventable. Better patient education, avoidance of polypharmacy, and clear communication between physicians, pharmacists, and patients, particularly during the transition between the inpatient to outpatient settings, can substantially reduce ADR risk.