Many extremely low birth weight (LBW) neonates now survive with intensive care. Their survival depends on fetal and neonatal adaptations of multiple organ systems, which represents a plasticity of development. Many extremely LBW neonates do not have severe lung immaturity, will breathe, and do not require surfactant treatment. The two clinically relevant modulators of this early lung maturation are antenatal corticosteroid treatments and fetal exposure to inflammation. Those same frequent fetal exposures also can mature the fetal innate immune system to become more proinflammatory. However, repeated fetal exposures to inflammatory mediators can blunt fetal inflammatory responses, which may minimize fetal injury. The brain of the extremely LBW neonate grows differently from that of the normal fetus such that brain volumes are different at term for the extremely LBW neonate and the term neonate. Regions of brain used to process information also differ from the child who was born very preterm and the child born at term. The adaptations that permit survival after very preterm birth may have adverse effects in later life. The biology of multiple organ system plasticities resulting from very preterm birth remains to be extensively explored.