The present article reviews the evidence base for psychosocial interventions provided to children in family-based out-of-home care that seek to improve children’s mental health, felt security, and/or the quality, strength or permanence of their attachment relationships. The review identified very few high-quality treatment trials carried out with this population. The interventions with the strongest demonstrated efficacy are Keeping Foster Parents Trained and Supported (KEEP) and Attachment and Biobehavioral Catchup (ABC). KEEP’s effectiveness has also been demonstrated in a community setting. Complex attachment- and trauma-related difficulties manifested by children in care following early maltreatment follow a long-term developmental course and have trait-like durability. Treatment trials should be designed as long-term studies, providing at least several years of post-treatment assessment. Practitioner points: Very few high-quality intervention trials have been conducted with children and adolescents in out-of-home care and/or their caregivers. The interventions with the strongest demonstrated efficacy are Keeping Foster Parents Trained and Supported (KEEP) and Attachment and Biobehavioral Catchup (ABC). Given the enduring nature of complex trauma- and attachment-related problems, treatment trials should include long-term follow-up mental health and relational measures. The effectiveness of treatments administered directly to adolescents are moderated by caregiver involvement and ‘buy-in’.