According to the WHO data, hypertension remains the first cause of death worldwide. In addition, considering the ageing of population, but also the development of countries in emerging area from Asia and Africa, the prevalence of high blood pressure is dramatically increasing. Hypertension Guidelines strongly support blood pressure reduction aimed to reach values lower than 130-80 mmHg by the utilization of the combination therapy. Unfortunately, the most relevant aspect related to a non-effective antihypertensive treatment is the lack of compliance. One of the possibilities to overcome this important limitation is the utilization of single pill combinations. More options are now available, and it is crucial to discuss possible differences in their therapeutic effectiveness. Moreover, a modern therapeutic strategy, in addition to blood pressure reduction, should include a pathophysiological approach targeting to consider all different hypertension-related alterations, including genetic determinants of the disease and its complications or gender differences, important aspects leading to personalized medicine. Finally, since hypertension is often associated to important cardiovascular diseases, it is necessary to tailor treatment according to the specific associated pathological conditions. In addition to classical complications including coronary artery disease or heart failure, it is now important to consider emerging aspects such as cognitive disorders and dementia.