Drug addiction is a syndrome of impaired response inhibition and salience attribution, which involves a complex neurocircuitry underlying drug reinforcement, drug craving and compulsive drugseeking and -taking behaviours despite adverse consequences. The continued elucidation of the neurobiological underpinnings of withdrawal symptoms, drug intake, craving, relapse, and co-morbid psychiatric associations has significantly boosted the development of new pharmacotherapies for the treatment of drug addiction. The present review will focus on recent advances in the development of innovative pharmacotherapeutic agents, which should promote long-lasting drug abstinence and longterm recovery, ensure satisfactory patient compliance, and have a good safety profile. First, the magnitude of the drug dependence problem will be presented by reviewing some of the most recent epidemiological data. Second, a short overview of the neurobiological substrates of drug craving and addiction will be presented. We will show that despite individual variation in the liability to the abuse of psychoactive substances, there is substantial commonality shared by drugs of abuse. The knowledge of these common mechanisms is critically important for the development of new therapeutic strategies. Third, pharmacological approaches and drug development strategies will be thoroughly discussed. The most promising strategies will be presented by reviewing key targets for drug discovery at both clinical and pre-clinical levels.