Adherence to antihypertensive therapy is critical to achieving adequate blood pressure control. About half of hypertensive patients do not take their drugs as directed and the physicians often underestimate this issue. Non-adherence has important public health economic implications (numbers of visits, diagnostic procedures, prescribed drugs) and, moreover, it results in increased morbidity and mortality rates. Poor adherence can have several patients and therapy related causes. Currently, multiple different direct and indirect methods to measure therapeutic adherence are available, but, in clinical practice, there is no cost-effective and simple one. Therapeutic drug monitoring (TDM), characterized by drug (or metabolites) concentration measurement in body fluids (blood or urine), is a cost-effective direct method to assess therapeutic adherence. Despite some limitations, TDM may decrease health costs, by reducing the number of visits and by identifying those patients who would undergo unnecessary invasive procedures. Moreover, TDM can be a new alternative method to identify patients with true resistant hypertension, improving the achievement of blood pressure control In this minor revision, we would assess poor therapeutic adherence in hypertensive population, analyzing the different direct and direct available methods, with emphasis on TDM.