Children with Down syndrome often have lower physical activity levels compared to their peers with typical development and face challenges such as medical co-morbidities, access issues and societal stigma, to being physically active. Physical therapists are experts in exercise prescription and physical activity and are thus uniquely qualified to successfully promote participation among children with Down syndrome in spite of inherent challenges. Our perspective is that a shift in physical therapy service delivery is needed. We suggest that physical therapists change the focus of their interventions for children with Down syndrome from underlying impairments such as low tone or joint laxity, or from developing motor skills in isolation and ‘correct’ movement patterns. Instead, physical therapists should allow the physical activity preferences and the environmental contexts of the children and adolescents they are working with to direct the treatment plan. In this way, physical therapy intervention becomes more child centered by concentrating on developing the specific skills and strategies required for success in the child’s preferred physical activity. In this paper, we consider the role of pediatric physical therapists in the United States, as well as in low- and middle- income countries, in promoting and monitoring physical activity in children with Down syndrome from infancy through adolescence. Examples of physical therapist interventions such as tummy time, movement exploration, treadmill training, bicycle riding and strength training are discussed, across infancy, childhood and adolescence, with a focus on how to successfully promote lifelong participation in physical activity.