Adverse drug reactions (ADR) have increasing clinical implications and are a permanent challenge for general practitioners. Data suggest that ADR cause 3 to 18% of all hospital admissions with potentially serious consequences. Polymedication, female sex, multiple pathologies with age-related changes are predisposing factors. Antihypertensive drugs with a low bioavailability, a high protein binding capacity and specific elimination pathways are particularly prone to pharmacokinetic interactions. ACE-inhibitors, atenolol, moxonidine and diuretics have few pharmacokinetic interactions. Calcium channel blockers and beta-blockers are associated with an increased risk of pharmacokinetic drug-drug interactions. Diltiazem and verapamil are particularly prone to interactions, as they strongly inhibit the elimination of drugs undergoing the CYP3A4 and P-glycoprotein pathways.