Delirium represents a common symptom in psychiatric diseases such as psychotic and affective disorders, organic illnesses and psychotropic substance abuse. The literature shows a high risk of developing psychosis in psychotropic substance abusers and a higher proneness to psychotropic substance abuse in people suffering from psychosis. The aim of this review is to discuss the relationship between substance abuse (cocaine, amphetamine, alcohol, cannabinoids, opioids, etc.) and the development of delirium, the way each molecule influences the pathogenesis of delirium, the neurochemical basis of delirium induced by psychotropic substances and the potential endophenotypes involved in a biologically plausible mechanism of mental diseases' pathogenesis.