Drug addiction presents a chronic relapsing disorder characterized by persistent drug-seeking and taking behaviors. Given the significant detrimental effects of this disease both socially and economically, a considerable research has been dedicated to understanding a number of issues in addiction including behavioral and neuro-pharmacological factors that contribute to the development of addiction, loss of self control and persistence of compulsive addictive behaviors. This review was designed to list out the drugs and factors which initiate and maintain dependence and how the relapse of these substances occurs in drug dependent persons.