Religious values are part of cultures, but spirituality is an internal dimension which may be present in varying degrees across all nations. As both cultural and spiritual factors are important in determining the pattern of alcohol consumption by individuals, it is important to study the relationships between them. The present systematic review aims to summarize the knowledge on the relationship between alcohol use and misuse, religiousness/spirituality and culture drawn from medical studies. Data from the medical literature to date indicate that for some racial and ethnic minorities a return to the traditional culture linked with concepts of spiritual or religious factors can produce a major degree of support for people trying to maintain abstinence from alcohol. This can be seen even in the worst environments. On the other hand, among the general population, religion and/or spirituality can play a positive role in the maintenance of abstinence, but a local heavy drinking culture is a strong risk factor for relapse. These factors are important and can be used for interventions and prevention strategies. However, possible mediating effects need to be explored further. It is likely that both types of intervention (classical medical treatment plus spiritual-based treatment) may work in individuals.