Parent–child separation occurs for many reasons, both involuntary and voluntary. We review the effects on children and youth of parent–child separation due to several of the most common reasons that are responsible for the growth in this family circumstance worldwide. These include early institutionalization; war, persecution, and conflict; separation during asylum; trafficking; conscription into armed conflict; and being left behind when parents migrate for economic or other reasons. Overall, the effects of parent–child separation are consistently negative on children's social-emotional development, well-being, and mental health. They are more severe when the separation is prolonged or accompanied by other forms of deprivation or victimization. Mitigating and protective factors include earlier stable family placement in the case of early institutionalization, parent–child communication and parenting quality, and community support in the host community. We conclude with an evaluation of group, school-based, and community-based interventions for children and youth affected by parent–child separation.