Alcohol and substance use disorder (ASUD) is a chronic condition featuring relapses and remissions. Due to their multifactorial nature, the causes of relapses in ASUD are not fully understood and it is important to update the information. Therefore, we aimed to provide an update on research examining factors associated with relapses, organized into sections. Factors such as early age of onset, dysfunction in the brain reward system, poor physical health, sleep disturbance, comorbid psychiatric disorders, severity of ASUD, craving, low self-efficacy, negative life events, and low socioeconomic status have been consistently shown to increase the relapse rate of ASUD. Conversely, factors such as positive family functioning, strong social support, treatment motivation and regular medication appear to decrease relapse rates. Studies on gender and genetic factors have yielded mixed results and no consistent relationship with relapses has been found. While pharmaceutical agents such as methadone, buprenorphine and naltrexone are effective in preventing relapse in opioid and alcohol use disorders; there are no agents proven to be effective in other substance use disorders. Psychotherapeutic approaches, including motivational interviewing, cognitive behavioral therapy, 12-step programs and contingency management have been demonstrated to be effective. The treatment of addiction to substances is intricate and necessitates biopsychosocial interventions. However, despite all treatments, high relapse rates indicate the necessity for social support and rehabilitation services. In the light of the data obtained, the factors affecting relapses in patients with ASUD can be determined and appropriate interventions and therapeutic approaches can be used to prevent relapses.