Drug addiction is a chronic disorder characterized by a high rate of relapse following detoxification. There are two main versions of the reinstatement model that are employed to study relapse to drug abuse; one based on the operant self-administration procedure, and the other on the classical conditioned place preference procedure. In the last seven years, the use of the latter version has become more widespread, and the results obtained complement those obtained in self-administration studies. It has been observed that the conditioned place preference induced by opioids, psychostimulants, nicotine, ethanol and other drugs of abuse can be extinguished and reinstated by drug priming or exposure to stressful events. Herein, the neuroanatomical and neurochemical basis of drug priming- and stress-induced reinstatement of morphine and cocaine, together with the molecular correlates of reinstatement behavior, are reviewed. Differences between the conditioned place preference and self-administration studies are also discussed. Evidence suggests that data of reinstatement with the CPP are to be viewed with caution until more extensive analysis of operant procedures has been performed, and that further research will undoubtedly improve our understanding of the neurobiological mechanisms of relapse to drug seeking.