The burden of cardiovascular (CV) disease remains high nowadays, despite the 
tremendous development in the therapeutic strategies that has occurred during 
the last 30 years. The growing focus on pharmacological strategies capable of 
interacting with key pathophysiological mechanisms has resulted in a better 
control of CV disease. The renin-angiotensin system (RAS) is involved in many 
pathophysiological processes underlying the development of major CV and renal 
diseases and, thus, it represents an 'ideal' target for the pharmacological 
treatment of these clinical conditions. Recently, in addition to the traditional 
therapeutic approaches, mostly based on the use of ACE inhibitors and/or 
angiotensin II type 1 receptor antagonists (angiotensin receptor blockers 
[ARBs]), the scientific and medical community have focused on a new therapeutic 
possibility to interfere with RAS activity. Indeed, the first compound of the 
new drug class of direct renin inhibitors, aliskiren, has been made available 
for clinical use. The therapeutic properties of aliskiren are of particular 
interest, since it interferes with the enzymatic activities of renin, the key 
rate-limiting step of the RAS cascade. This unique mechanism of action, e.g. 
occupation of the renin active site, provides an 'upstream' modulation in the 
RAS enzymatic-proteic cascade. This results in an inhibition of the biological 
properties of renin to promote the cleavage of the angiotensin I peptide from 
the angiotensinogen substrate.Clinical studies have demonstrated that the use of 
aliskiren provides antihypertensive efficacy comparable with, or even superior 
to, that observed with other classes of antihypertensive drugs. Also, the 
addition of aliskiren to different antihypertensive strategies results in a 
further significant increase in blood pressure (BP) reduction than those 
achieved with monotherapy based on diuretics, calcium-channel antagonists, ACE 
inhibitors and ARBs. The overall safety and tolerability of aliskiren are 
comparable with other classes of antihypertensive drugs and almost overlap with 
placebo. Recent evidence also demonstrates that aliskiren is effective in 
promoting the regression of organ damage (e.g. microalbuminuria and left 
ventricular hypertrophy), beyond its BP-lowering properties and in addition to 
standard therapies, including ARBs. An ambitious programme of clinical 
development of this modern antihypertensive drug will investigate whether 
aliskiren may further limit the incidence of major CV and renal events in 
hypertensive patients with co-morbidities, treated with the available 
therapeutic strategies, including ACE inhibitors and ARBs.