In the process of developing a series of reports and briefs based in existing theory and research on toxic stress, self-regulation, and self-regulation interventions, a number of gaps in the existing knowledge base were identified. Research shows the value of interventions to strengthen self-regulation, yet there are many unanswered questions. This brief addresses key gaps in interventions and intervention research examined in a recent literature review. In addition, the brief highlights work needed in intervention design and development to enhance programs intended to strengthen self-regulation, particularly those that serve vulnerable children and youth. We expect that this brief will be of greatest interest to prevention scientists, funders, and policy-makers. (author abstract)