Hypoglycemia is a common condition in the newborn period. Several intrinsic and extrinsic factors play a role in the degree/duration of hypoglycemia. Multiple thresholds have been proposed as a potential point whereby hypoglycemia may have short and long-term adverse effects. Rather than a “numerical” threshold, treatment approaches should be individualized and tailored to the etiology, symptoms, and neonatal underlying conditions. Hyperglycemia in the newborn period is commonly seen in preterm infants and can exert gluco-toxic effects in organs at critical periods of development. Considering the peripheral insulin resistance (IR) of prematurity and contributing factors is key to achieving euglycemia.