Hematopoietic stem-cell transplant (SCT) is increasingly used to treat children with cancer, and survival following SCT is improving. One predominant consequence of childhood cancer therapy is increased physical morbidity, which is worse in pediatric SCT recipients compared with children treated with chemotherapy or radiation alone. There are many factors that contribute to exercise intolerance and reduced physical function during the pretransplant, peritransplant, and posttransplant phases. These include side effects from chemotherapy or radiation, excessive immobility due to bed rest, infections, the negative effects of immunosuppressants, and graft vs host disease, all of which can impair cardiorespiratory fitness, muscle strength, and muscle function. Few studies have investigated the effects of exercise in childhood SCT recipients. In a small number of published studies, exercise interventions have been demonstrated to improve cardiorespiratory fitness, preserve or increase muscle mass, and improve muscle strength in children following SCT. The use of exercise as medicine may be a noninvasive and nonpharmaceutical treatment to target physical complications post-SCT. Researchers and health-care professionals should work together to develop exercise prescription guidelines for this unique and important population.