Placental insufficiency is a process leading to progressive deterioration in placental function and a decrease in transplacental transfer of oxygen and nutrients to the fetus. The resulting fetal hypoxemia is the major stimulus involved in the reduction in fetal growth as an attempt to reduce metabolic demands by the growing fetus. Fetal growth restriction (FGR) is the second cause of perinatal death after prematurity and can complicate up to 6% of all pregnancies. It is becoming apparent that its occurrence has major impacts on the fetus and placenta with consequences on the cardiovascular, metabolic and neurological development up to adulthood. We are just starting to unveil some of the basic mechanisms involved in this complex adaptation that may lead to reprogramming of fetal organs development mostly the heart, pancreas, lungs and brain. It is becoming clear that future research is needed to develop strategies to improve antenatal detection of FGR, in addition to reduce the risk of abnormal neurodevelopment during childhood, and onset of common diseases in adulthood following pregnancies complicated with placental insufficiency.