This article presents findings from a mixed-methods study exploring child welfare agency practices addressing children with prenatal substance exposure and their families. Data sources include: (a) interviews with 159 professionals in child welfare; (b) surveys with 271 professionals in child welfare; and (c) a systematic review of state and local child welfare documents guiding processes in the five states in the study sample. Findings from descriptive statistics of survey data, grounded theory analysis of interviews, and content analysis of documents suggest practices center on infants identified by hospitals as affected by prenatal substance exposure. Without practice guidance and access to treatment services, the needs of older children whose prenatal exposure to substances, including alcohol and other types of legal and illegal substances, is not recognized at birth may be overlooked.