Life traumatic experiences are major health problems in different communities. Early trauma exposures such as physical and sexual abuse, and midlife traumatic events like exposing to disasters are predisposing and precipitating risk factors for many psychiatric disorders, although many people facing to trauma may not show any problematic symptoms and are quite resilient. Neuropsychiatric evidences show that exposing to a traumatic event, especially in childhood, may render structural and functional changes of neural system and brain, leading to psychiatric disorders including major depressive disorder, post-traumatic stress disorder (PTSD), schizophrenia and substance use disorder (SUD). The relationship between trauma exposure and SUD has been well established. About 2/3 of substance users have a history of exposing to trauma and alcohol and substance use are leading co-morbid conditions in male and female cases of PTSD. There are many reasons people exposing to trauma tend to use substances, like self-medication, avoiding negative experiences and emotions, recreation and re-experience of traumatic events and etc. This review indicates of some reasons of this comorbidity.