The 2011 U.S. Government Evidence Summit on Protecting Children Outside of Family Care brought together leading researchers and technical experts to assess the available evidence to inform policies, strategies, and programs relevant to protecting children outside of family care in lower and middle income countries. While child vulnerabilities are clearly multi-dimensional, global programs are often fragmented, as exemplified by the multitude of U.S. agencies with responsibilities for global child protection. Leading multilateral, bilateral, government, and nongovernmental agencies are now embracing a more systemic approach consistent with a more holistic orientation towards children's needs. A case is made in this paper for a more coordinated, evidence-based strategy for addressing the needs of children who are abandoned, abused, or severely neglected. Although a new U.S. Action Plan for Children in Adversity will emerge from the work of the summit, it must be acknowledged that there is a dearth of rigorous studies to complement information gleaned from practitioner experience, agency reports, case studies, and anecdotal evidence, with higher quality studies weighted towards children who can be captured by household surveys that too often miss large numbers of children outside of family care (e.g., those trafficked, abandoned). Although there are challenges in conducting rigorous, ethically responsible research in this area, there is also a cost of inaction. There is a need for sufficient funding for research and high quality evaluation to develop a strong empirical base to support many of the practices in the field, thereby assisting in the cost-effective and more innovative utilization of other program funds. The Summit's findings also highlight the importance of the establishment of appropriate knowledge transfer and learning mechanisms across communities of practice.