Glucose is the most important foetal energy substrate. At birth the transplacental transfer of substrates is terminated. Before the start of breastfeeding the newborn infant must produce its own glucose particularly for the need of the central nervous system. Neonatal hypoglycaemia commonly occurs in risk groups such as immature and low birth weight infants, infants of mothers with diabetes and infants born large for gestational age. Our data show that extremely immature infants can also produce their own glucose during the first day of postnatal life. Although their stores of depot fat are limited, they also have a capacity for lipolysis. Infants of diabetic mothers have unimpaired lipolysis in spite of hyperinsulinaemia. This may represent a mechanism to compensate for the reduced rate of glucose production in these infants. The number of infants born large for gestational age is increasing in several countries partly consequent to increases in maternal weight. We have shown that foetal weight depends on maternal glucose production, which in turn is related to parameters associated with maternal fat mass. Like infants born small for gestational age, those born large for gestational age are at risk for metabolic disease later in life. Owing to a high fat mass these infants have a high rate of lipolysis, which can be one reason underlying the reduced insulin sensitivity seen already during the first day of life.