Objectives: This article reviews the available evidence regarding the efficacy, effectiveness, ethics, and sustainability of approaches to strengthen systems to care for and protect children living outside family care in low- and middle-income countries. Method: For trafficked children, children of and on the street, children of conflict/disaster, and institutionalized children, a systems framework approach was used to organize the topic of sustainable approaches in low- and middle-income countries and addresses the following: legislation, policies, and regulations; system structures and functions (formal and informal); and continuum of care and services. The article draws on the findings of a focal group convened by the U.S. Government Evidence Summit: Protecting Children Outside of Family Care (December 12-13, 2011, Washington, DC), tasked with reviewing the literature on systems, strategies, and interventions for sustainable long-term care and protection of children with a history of living outside of family care in low- and middle-income country contexts. The specific methodology for the review is described in the commentary paper (Higgs, Zlidar, & Balster, 2012) that accompanies these papers. Results: For the most part, the evidence base in support of sustainable long-term care for the populations of interest is relatively weak, with some stronger but unreplicated studies. Some populations have been studied more thoroughly than others, and there are many gaps. Most of the existing studies identify population characteristics, needs, and consequences of a lack of systemic services to promote family-like care. There is some evidence of the effectiveness of laws and policies, as well as some evidence of service effectiveness, in improving outcomes for children outside of family care. Conclusions: Despite the weaknesses and gaps of the existing research, there is a foundation of research for going forward, which should focus on developing and implementing systems for these most vulnerable children. The evidence reviewed indicates that child protection systems should aim for appropriate, permanent family care (including reunification, adoption, kinship care, or kafalah) for children in order to secure the best environment for a child's developmental prospects. Evidence also suggests that the quality and duration of care, including both permanent family care and alternative care, are important regardless of setting. The diversity of political, socioeconomic, historical, regional, community, and cultural contexts in which child protection systems operate need to be taken into account during programming and research design.