Volatile chemicals used widely as solvents can produce acute effects on the nervous system and behavior after inhalation exposure, and many are subject to abuse. This review considers the nature of the acute effects of volatile organic solvents by comparing their actions to those of classical CNS depressant drugs such as the barbiturates, benzodiazepines and ethanol. Like CNS depressant drugs, selected inhalants have been shown to have biphasic effects on motor activity, disrupt psychomotor performance, have anticonvulsant effects, produce biphasic drug-like effects on rates of schedule-controlled operant behavior, increase rates of punished responding, enhance the effects of depressant drugs, serve as reinforcers in self-administration studies and share discriminative stimulus effects with barbiturates and ethanol. Toluene and 1,1,1-trichloroethane, as well as subanesthetic concentrations of halothane, have been the most extensively studied; however, it is unclear whether important differences may exist among solvents in their ability to produce a depressant profile of acute effects. The possibility that selected solvents can have acute effects similar to those of depressant drugs may shed light on the nature of their acute behavioral toxicology and on their abuse.