Preclinical studies and clinical trials carried out within the past few years have provided a premise that gamma-aminobutyric acid (GABA) transmission and GABA(B) receptors play a modulatory role in the mechanism of action of different drugs of abuse. The present review summarizes the contribution of GABA(B) receptors to the rewarding, locomotor and discriminative stimulus properties of drugs of abuse and their withdrawal symptoms in laboratory animals. It also reviews the current knowledge about the GABA(B) receptor ligands in clinical trials, with a focus on their effects on presentation of the drug-associated cues and withdrawal-induced drug craving.