A highly selective ẞ1-adrenergic receptor antagonist, nebivolol has a unique pharmacologic profile from other medications in its class. Nebivolol causes nitric oxide-mediated vasodilation in addition to cardioselectivity mediated by ẞ1 receptor blockage by activating endothelial nitric oxide synthase via 3 agonism. Contrary to other vasodilatory -blockers (carvedilol, labetalol), which work by blocking -adrenergic receptors, this vasodilatory mechanism is unique. In the US and Europe, nebivolol is authorized for the treatment of hypertension and heart failure, respectively. Although -blockers are not advised as the first-line therapy for the treatment of essential hypertension according to the most recent US guidelines, with a relatively low risk of adverse effects, nebivolol has demonstrated comparable efficacy to presently indicated medications in decreasing peripheral blood pressure in persons with hypertension. Compared to other -blockers, nebivolol also has favorable effects on central blood pressure. Nebivolol may also be helpful for patients who have suffered erectile dysfunction while taking other -blockers, according to clinical studies. Here, we discuss nebivolol's pharmacological profile, the clinical evidence that supports its use as a monotherapy, add-on therapy, and combination therapy for hypertension, as well as the information pointing to its beneficial effects on heart failure and endothelial dysfunction. There are some analytical methods for the analysis of the drug in the biological fluids and pharmaceutical preparations. In this work, we have collected these methods with the aim to present the different options for the nebivolol determination.