Salvia divinorum L. (Lamiaceae) has been used for centuries by the Mazatecan culture and has gained popularity as a recreational drug in recent years. Its potent hallucinogenic effects seen in case reports has triggered research and led to the discovery of the first highly selective non-nitrogenous κ opioid receptor agonist salvinorin A. This review critically evaluates the reported pharmacological and toxicological properties of S. divinorum and one of its major compounds salvinorin A, its pharmacokinetic profile, and the analytical methods developed so far for its detection and quantification. Recent research puts a strong emphasis on salvinorin A, which has been shown to be a selective opioid antagonist and is believed to have further beneficial properties, rather than the leaf extract of S. divinorum. Currently animal studies show a rapid onset of action and short distribution and elimination half-lives as well as a lack of evidence of short- or long-term toxicity. Salvinorin A seems to be the most promising approach to new treatment options for a variety of CNS illnesses. However, many further investigations are necessary to fully understand and elucidate the various medicinal properties of the plant itself and to provide the legislative authorities with enough information to cast judgement on S. divinorum.