Aim: To assess the efficacy of drugs directly acting on alpha- and beta-adrenergic receptors in the treatment of patients suffering from tobacco or alcohol use disorder. Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies were identified through PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials and clinicaltrial.gov. We selected only randomized controlled trials with adult patients with tobacco or alcohol use disorders according to DSM-5 criteria. Interventions included any molecule having a direct pharmacological action on alpha- or beta-adrenergic receptors (agonist or antagonist). Comparators were placebo or other validated pharmacotherapies. The duration of the intervention was a minimum of 1 month, with 3 months of follow-up. Measurements included smoking cessation for tobacco; for alcohol, we selected abstinence, alcohol consumption (drinks per day or week) and heavy drinking days (HDD). Ten studies with tobacco and six with alcohol use disorder were included in the qualitative synthesis and fifteen studies in the quantitative analysis. Results: We found that clonidine, an alpha-2 agonist, significantly increased smoking abstinence [relative risk = 1.39 with a 95% confidence interval (CI) = 1.04, 1.84]. Beta-blockers had no significant effect on smoking abstinence. The alpha-1 antagonists prazosin and doxazosin decreased alcohol consumption [SMD = -0.32 (-0.56, -0.07)] but had no effect on abstinence or HDD. Conclusions: The noradrenaline system may represent a promising mechanism to target in tobacco and alcohol use disorders.