Blood viscosity plays a key role in regulating microvascular flow and alterations of hemorheological variables can lead to hyperviscosity, thus favoring the occurrence of occlusive thrombotic events. In the last few years an association between alterations in the hemorheologic profile and the severity of blood flow disturbances has been emphasized in several clinical and experimental conditions, possibly contributing to a better understanding of the pathophysiology of vascular disorders. The presence of alterations in hemorheological variables proved to be associated in several studies with an increased risk of cardiovascular disease and a higher mortality. The role of blood viscosity has also been analyzed in retrospective studies, which demonstrated that alterations in some hemorheological variables may increase the incidence of embolic events in patients with atrial fibrillation and may influence the responsiveness to antiplatelet drugs in patients with acute coronary syndromes. Recently, alterations of some hemorheological parameters were shown to be associated with complete occlusion of coronary arteries, favoring the occurrence of myocardial infarction with ST-segment elevation. In patients with this clinical condition, an increase in blood viscosity and some of its determinants was associated with increased infarct size and worse acute left ventricular dysfunction. Finally, the results of some observational clinical studies have shown that alterations of hemorheological variables may help to explain the pathophysiological mechanisms of some clinical disorders in which microvascular damage has been demonstrated, such as idiopathic sudden sensorineural hearing loss, retinal vein occlusion, and systemic sclerosis.