Families that contend with the losses, disruptions, and hardships occasioned by homelessness often experience dispersal of children as well. Although a federal initiative on homeless families identified family preservation as a focus of intervention development, there is little research to guide service efforts. This qualitative study of mother–child separations in homeless families with maternal mental health and/or substance use problems identifies precursors of separations (precarious housing, turbulent relationships, substance abuse by mothers and others, institutional confinement, and children’s needs) and examines how mothers’ responses to these events and conditions interact with social and institutional contexts to shape variations in the course and outcome of separations. Implications for research, services, and policies affecting homeless families are discussed.