Magnesium decreases the intensity of some drug-induced dependences (e.g. opiates, nicotine, cocaine, amphetamine, ethanol, etc.). The main mechanism involved is a decreasing activity of central glutamatergic synapses, especially those involved in the reward system. There are many particularities of action for each drug dependence. Apart from the effects during emerging dependence, magnesium ions administered only during the withdrawal syndrome decrease the intensity of clinical symptoms. In some cases, Mg2+ decreased the relapse and reinstatement of cocaine and amphetamine intake. Administered alone, in the absence of any abused drug, Mg2+ has moderate stimulatory effects on the reward system and reinforcement, without inducing dependence. The existent data stress a modulatory role of Mg2+ in some drug-induced dependences. Therapeutic administration of magnesium decreases nicotine dependence and cocaine/amphetamine self-administration.