Infants constitute a large and increasing proportion of youth in out-of-home placement. These infants have very high rates of medical illnesses, developmental delays, and substantial risks for psychopathology. They receive varying amounts of services from a complex and poorly integrated service system that includes four principal service sectors: the child welfare, medical, early intervention, and mental health service sectors. These service systems are currently undergoing major changes in their policies, organization, and financing, such as the introduction of managed care into the child welfare system. In this article, we provide an overview of what is known about infants in out-of-home placement. We then summarize approaches to infant mental health assessment and intervention from a comprehensive perspective that addresses the infants' multiple problems and acknowledges that they need to receive services from multiple systems that are undergoing rapid change. We conclude by highlighting a number of critical areas in need of research.