Addiction is a complex psychiatric disorder characterised by a spectrum of compulsive drug-seeking behaviours and a persistent tendency to relapse (return to drug taking) even after prolonged periods of abstinence. The most commonly used models for the study of drug reward and dependence involve drug self-administration paradigms in mice, rats or monkeys. However, assays using drug-induced conditioned place preference (CPP) have become increasingly popular due in part to the non-invasive and simple nature of the procedure. Using self-administration and conditioned place preference assays we and others have shown that zebrafish show reinforcement responses to common drugs of abuse including ethanol, nicotine, amphetamine, cocaine and opiates and are thus a suitable model for analysis of factors affecting ‘reward’. Our work reviewed here further demonstrates that on prolonged exposure to nicotine or ethanol, zebrafish show persistent drug seeking in the face of adverse stimuli, and that drug seeking can be reinstated following extinction using stimuli that induce reinstatement in mammalian models and relapse in humans. Thus our work supports the use of zebrafish as a model system for the study of genetic/molecular mechanisms underlying vulnerability to drug dependence and addiction.