A relapsing-remitting course is very common in patients with an Alcohol Use Disorder (AUD). Understanding the determinants associated with alcohol resumption remains a formidable task. This paper examines relapse determinants based on a systematic review of recent alcohol literature (2000-2019). Relevant databases were consulted for articles that contained information about specific relapse determinants and reported statistical significance of each relapse determinant in predicting relapse. Relapse was broadly defined based on the characterization in the included articles. From the initial identified 4613 papers, a total of 321 articles were included. Results encompass multiple relapse determinants, which were ordered according to biopsychosocial and spiritual categories, and presented, using a descriptive methodology. Psychiatric co-morbidity, AUD severity, craving, use of other substances, health and social factors were consistently significantly associated with AUD relapse. Conversely, supportive social network factors, self efficacy, and factors related to purpose and meaning in life, were protective against AUD relapse. Despite heterogeneity in different methods, measures, and sample characteristics, these findings may contribute to a better therapeutic understanding in which specific factors are associated with relapse and those that prevent relapse. Such factors may have a role in a personalized medicine framework to improve patient outcomes.