Physical activity during treatment is an important way to promote health and quality of life for children with cancer. Nurses play a pivotal role in creating and supporting physical activity interventions. In this chapter we present information on the impact of a cancer diagnosis and treatment on a child’s activities and physical functioning. In addition, we offer evidence that nurses can readily translate into their practice to promote physical activity in this vulnerable population. By applying principles of precision health offered in this chapter, the nurse can identify the child, family, disease, and environmental factors that influence physical activity and use this information to develop successful interventions across the childhood cancer trajectory. The chapter also offers insights into the role that nurses play in mobilizing resources to address barriers to physical activity, including multidisciplinary care and family influences. Finally, we examine the state of the science about physical activity and childhood cancer and suggest avenues for nursing research to expand the frontier of this important field.