Relevant papers published in peer reviewed journals in the past 2 decades were identified and screened to abstract pertinent information. Substance dependence/addiction, involving both a common brain reward mechanism and longer-lasting molecular and cellular changes, is a preventable chronic, relapsing brain disease and as such a public health problem. Physical and psychological dependence, characterized by withdrawal syndrome, are now given less weight compared with compulsive behaviour and uncontrolled use of drugs in the comprehension of addiction. The challenging components of drug addictions, including counteradaptation, sensitization, abstinence, craving and relapse need further neurobiological and non-neurobiological exploration and understanding, which may be possible through the use of advanced imaging and genetic techniques and animal models of drug addiction together with relevant human studies.