Essential hypertension is a polygenic disease involving a major contribution of various environmental factors. It is therefore not surprising that antihypertensive medications, whatever their mechanism(s) of action, only normalize the blood pressure for a fraction of hypertensive patients when administered as monotherapies. It is unfortunately not possible to predict with any degree of certainty which type of blood pressure-lowering agent is the most appropriate for a given patient. Although very attractive, genetic mapping is not really helpful in selecting a treatment for any individual patient. In most patients the association of two medications having different impacts on the cardiovascular system is necessary to normalize blood pressure. Fixed-low-dose combinations are becoming increasingly popular as first line treatment as they increase the probability of bringing the patient's blood pressure under control while minimizing the incidence of dose-dependent adverse effects.