Recent reports of interactions between alcohol and benzodiazepines, tricyclic and tetracyclic antidepressants during their acute concomitant use are reviewed. Acute ingestion of alcohol (ethanol) with tranquilizers or hypnotics is responsible for several pharmacokinetic interactions that can have significant clinical implications. In general, metabolism of these drugs is delayed when combined with alcohol but some reports have suggested otherwise. The amount of alcohol consumed, the presence or absence of liver disease, and differences in the dosage and administration of these drugs may account for the observed discrepancies. In recent years, the cytochrome P450 (P450 or CYP) isoenzyme that catalyses the metabolism of these drugs has also been identified. However, since changes in the pharmacogenetic metabolism of benzodiazepines and tricyclic and tetracyclic antidepressants are mainly governed by CYP2C19 and CYP2D6, caution is needed when used together with alcohol.