The endocannabinoid system has been involved in a variety of physiological functions, including the control of nociception, motor behaviour, learning/memory, reward, neuroprotection, food intake and metabolism. This system is mainly activated in response to external stimuli to help stablish the steady-state homeostasis of other neurotransmitters and mediators. Recent studies have involved the endocannabinoid system in the common neurobiological substrate underlying drug addictive processes. This system participates in the primary rewarding effects of cannabinoids, nicotine, alcohol and opioids through the release of endocannabinoids in the ventral tegmental area. Endocannabinoids are also involved in the motivation to seek the drug by a dopamine-independent mechanism demonstrated for psychostimulants and opioids. The endocannabinoid system participates as well in relapse to drug-seeking behaviour by mediating the motivational effects of drug-related environmental stimuli and drug re-exposure. In agreement, clinical trials have revealed the effectiveness of the CB1 cannabinoid antagonist rimonabant to obtain smoking cessation. CB1 cannabinoid antagonists could represent a new generation of compounds to treat drug addiction.