This critical appraisal of a Cochrane Review assesses the efficacy of ketamine for treating unipolar major depressive disorder. The review included 31 randomised controlled trials involving ketamine. Results indicate that intravenous (i.v.) ketamine significantly improves antidepressant response compared with i.v. saline and, to a lesser extent, i.v. midazolam within 24–72 h. However, the evidence is constrained by performance bias owing to masking (‘blinding’) concerns and study heterogeneity, necessitating further robust research to confirm ketamine’s clinical potential.