Vascular and associated ventricular stiffness is one of the hallmarks of the aging cardiovascular system. Both an increase in reactive oxygen species production and a decrease in nitric oxide (NO) bioavailability contributes to the endothelial dysfunction which underlies this vascular stiffness, independent of other age related vascular pathologies such as atherosclerosis. The activation/upregulation of arginase appears to be an important contributor to age-related endothelial dysfunction by a mechanism that involves substrate ( L-arginine) limitation for NOS 3 and therefore NO synthesis. Not only does this lead to impaired NO production but might contribute to the enhanced production of reactive oxygen species by NOS. While arginase abundance might be increased in vascular aging models, it appears that post-translational modification by S-nitrosylation of the enzyme enhances its activity as well. The S-nitrosylation is mediated by the induction of iNOS in the endothelium. Furthermore, arginase activation might contribute to aging-related vascular changes by mechanisms that are not directly related to changes in NO signaling, including polyamine-dependent vascular smooth muscle proliferation and collagen synthesis. Taken together, arginase may represent an as yet elusive target for the modification of age-related vascular and ventricular stiffness contributing to cardiovascular morbidity and mortality.