One of the consequences of genetic impairments in early childhood is their long-term effect on children's developmental skills in communication, learning, and adaptive behaviors. Functional assessment provides families and clinicians with a common language for describing a child's strengths and limitations in self-care (feeding, dressing, grooming, bathing, continence), mobility, and communication/social cognition. The National Center for Medical Rehabilitation Research described a model of disablement that includes five dimensions: pathophysiology, impairment, functional limitations, disability, and societal limitations. Using this framework, along with the Functional Independence Measure for children, the WeeFIMเฎพ, we describe functional strengths and challenges in children with Down syndrome, spina bifida, congenital limb anomalies, congenital heart disease, urea cycle disorders, severe multiple developmental disabilities, and Di-George malformation sequence. We also briefly describe several pediatric functional/adaptive assessment instruments used by developmental professionals (Battelle Developmental Inventory, Vineland Adaptive Behavior Scales, Amount of Assistance Questionnaire). By tracking functional status, health professionals can prioritize secondary and tertiary prevention strategies that optimize self-care, mobility, communication, and learning. When functional limitations interfere with the acquisition of these essential skills, family and community support programs can be maximized. Am. J. Med. Genet. (Semin. Med. Genet.