This work reviews preclinical and clinical studies published during the past two decades on the cellular and behavioral effects of commonly misused solvents. In animals, acute solvent exposure produces motor impairment and antidepressant- and anxiolytic-like effects. Human intoxication from misusing solvents is similar to that of ethanol; however, hallucinations and sudden sniffing death may occur at high solvent concentrations. Among chronic misusers, there is evidence of impaired memory, increased prevalence of psychiatric disorders, and neurological damage. Solvents facilitate inhibitory neurotransmission and block excitatory mechanisms. Toluene, in particular, increases brain dopamine levels and its effects occur at concentrations that do not dissolve cell membranes; therefore, neuronal damage is not an immediate, unavoidable consequence of solvent misuse.