Alcohol and other substance use disorders are complex problems with multiple variables and determinants, requiring a multidimensional approach to prevention and treatment. A robust body of research shows that religiosity and spirituality (R/S) play a prominent role in these disorders; however, how to apply this knowledge remains unclear. We present practical guidelines on how to integrate R/S into substance use prevention and treatment in an ethical, evidence-based manner. These guidelines have been endorsed by prominent academic leaders in these topics and by health associations affiliated with the three major Brazilian religions. The integration of R/S is part of a respectful, person-centered, interdisciplinary approach, which imposes neither religious beliefs nor secular worldviews. The most critical interventions include collecting a history of spiritual and religious beliefs, practices, and experiences and evaluating how these may be used positively in treatment. It is also essential that health professionals are encouraged to value and respect the R/S of patients, and that religious groups recognize that professional and technical interventions can make a valuable contribution to preventing and treating these disorders. determinants RS R S (R/S however unclear ethical evidencebased evidence based manner religions respectful personcentered, personcentered person centered, centered person-centered worldviews practices patients