Alignment and shaping of the musculoskeletal system occur during each body position that infants experience while in neonatal intensive care. Neonatal nurses and physical therapists can play a major role in designing, modeling, and teaching positioning strategies that promote skeletal integrity, postural control, and sensorimotor organization. Musculoskeletal maturation processes and adverse musculoskeletal consequences are reviewed with an emphasis on clinical implications for neonatal care, discharge teaching, and follow-up. Recommendations are offered for neonatal positioning procedures to prevent extremity malalignment, skull deformities, and gross motor delay.