The optimal management of hypertensive patients requires accurate evaluation of cardiovascular risk factors and co-morbidities. The therapeutic approach to hypertension may, in fact, be significantly different according to associated conditions. Among them, the presence of coronary heart disease, heart failure, cerebrovascular disease, chronic kidney disease, and specific age groups deserve special attention. In this chapter, the initial diagnostic work-up, the thresholds and targets for treatment, and the preferred drugs in specific conditions/co-morbidities will be briefly discussed.