Background <p>Out-of-hospital cardiac arrest is considered a major public health issue with an incidence of 67–170 per 100.000 inhabitants in Europe. Sufficient coronary perfusion pressure is a requisite for successful defibrillation and return of spontaneous circulation (ROSC). Although epinephrine (E) was found to increase ROSC and hospital survival when compared to placebo, its role in shockable arrest is under debate due to the absence of favorable neurological outcome.</p> Objective <p>Norepinephrine (NE) increases coronary perfusion pressure and may be an alternative for epinephrine because of differences in affinity in alpha- and beta- adrenergic receptors.</p> Methods <p>An extensive literature search was conducted in PreMedline, Medline, Embase and Cochrane electronic databases. All original studies (randomized controlled trials, experimental and observational studies, including case-reports) were included; guidelines, (editorial) reviews and commentaries were excluded, no date constraints were applied. Articles were included in the literature review if they described intra-arrest administration of norepinephrine and contained at least an abstract in English, French, or German.</p> Results <p>A total of 3308 articles were screened after deduplication. Following initial title/ abstract screening, full-texts analysis was performed in <i>n</i> = 46 studies. A total of 18 articles were included, consisting of 5 human and 13 animal studies. Norepinephrine appears to optimize macrocirculatory-and myocardial hemodynamics, increased regional cerebral blood flow and might improve survival.</p> Conclusion <p>Norepinephrine has shown several beneficial effects when administered during shockable cardiac arrest in animal studies, with similar signals suggested in human studies. Despite the limited evidence, norepinephrine appears to offer potential advantages over epinephrine in terms of multiple haemodynamic parameters and possible survival.</p>