The management of hypertension remains a difficult task, despite the availability of an increasing number of medications that decrease blood pressure by different mechanisms. In order to achieve a blood pressure less than 140/90 mmHg, most hypertensive patients require the co-administration of two or more drugs from different therapeutic classes. This explains why fixed-dose combinations are becoming increasingly popular. Combining drugs with different impacts on the cardiovascular system makes it possible to maximise the antihypertensive efficacy of the treatment regimen. The combination of very low doses of drugs that exhibit dose-dependent side effects leads to a marked gain in efficacy, with indiscernible side effects. During recent years, very-low-dose combinations have been developed. These combinations are very promising because of their excellent efficacy and tolerance profile. This has led to the recognition that such combinations might be a valuable option with which to initiate treatment in hypertensive patients.