Hypertension is a major preventable risk factor for atherosclerosis and ischemic heart disease. Although modern and effective antihypertensive drugs are available, most patients remain with a suboptimal blood pressure control. Most hypertensive patients will need a combination of antihypertensive agents to achieve the therapeutic goals – recent guidelines recommend initiating treatment with two drugs in those patients with a systolic blood pressure >20 mmHg and/or a diastolic blood pressure >10 mmHg above the goals, and in those patients with high cardiovascular risk. In addition, approximately 25% of patients will require three antihypertensive agents to achieve the therapeutic targets. In this review, we analyse the latest information available regarding the treatment of hypertension with combination therapy.