Substances with psychotomimetic properties such as cocaine, amphetamines, hallucinogens and cannabis are widespread, and their use or abuse can provoke psychotic reactions resembling a primary psychotic disease. The recent escalating use of methamphetamine throughout the world and its association with psychotic symptoms in regular users has fuelled concerns. The use of cannabis and cocaine by young people has considerably increased over recent years, and age at first use has dramatically decreased. There is some evidence that cannabis is now on the market in a more potent form than in previous decades. Furthermore, a large number of studies have reported a link between adolescent cannabis use and the development of stable psychosis in early adulthood. The situation is further complicated by the high rates of concomitant substance use by subjects with a psychotic illness which, especially in young users with an early-phase psychotic disorder, can make diagnosis difficult. This paper reviews the literature concerning the properties of psychotogenic substances and the psychotic symptoms they can give rise to, and discusses the association between substance abuse and psychosis with particular emphasis on the differential diagnosis of a primary and substance-induced psychotic disorder. The findings of this review indicate that psychosis due to substance abuse is commonly observed in clinical practice. The propensity to develop psychosis seems to be a function of the severity of use and dependence. From a phenomenological point of view, it is possible to identify some elements that may help clinicians involved in differential diagnoses between primary and substance-induced psychoses. There remains a striking paucity of information on the outcomes, treatments, and best practices of substance-induced psychotic episodes.