Scientific evidence suggests substance-use disorder (SUD)-focused self-help group involvement is a helpful adjunct to SUD treatment, yet significant knowledge gaps remain. The principal aim of this review is to highlight areas of knowledge deficit and their implications for research and practice. To accomplish this, evidence regarding whether self-help group involvement is effective, for whom, and why, is reviewed. The appropriateness of self-help groups for certain subpopulations is considered with respect to psychiatric comorbidity, religious orientation, gender, and age. An increasingly rigorous body of evidence suggests consistent benefits of self-help group involvement. Regarding subpopulations, current evidence suggests non- or less-religious individuals benefit as much from self-help groups as more religious individuals and women become as involved and benefit as much as men. However, participation in, and effects from, traditional self-help groups for dually diagnosed patients may be moderated by type of psychiatric comorbidity. Some youth appear to benefit, but remain largely unstudied. Dropout and nonattendance rates are high, despite clinical recommendations to attend. Clinicians can significantly influence the effectiveness of self-help, but optimal methods and duration of facilitation efforts need testing. Greater understanding of the reasons why many do not attend or drop out would benefit facilitation efforts.