Human infants require n-6 and n-3 long-chain polyunsaturated fatty acids (LCPUFA), derivatives of the essential fatty acids, linoleate (n-6) and linolenate (n-3), for growth and neural development. Animals fed diets deficient in the essential fatty acids have low neural LCPUFA and behavioral changes that imply adverse effects on brain function. Studies of animals deficient in essential fatty acids have provided the rationale and outcomes for studies to determine whether human infants need dietary LCPUFA. After including n-3 LCPUFA in formula, preterm infants showed higher sensory function (retinal responses to light, visual acuity), visual attention characteristic of higher maturity during infancy, and higher scores on test of global development (6- and 12-mo Bayley Mental Developmental Index). In term infants, some but not all studies found higher visual acuity, 4-mo Brunet-Lezine psychomotor development, and 10-mo means-end problem solving with LCPUFA-containing formulae compared to formulae in general use. Because preterm infants have lower LCPUFA accumulation at birth than term infants, it may be easier to show benefits of dietary LCPUFA for neural development in the former group. In addition to low gestational age, other variables may influence LCPUFA accumulation at birth and determine whether a particular group of infants will respond to dietary LCPUFA. One current challenge is to identify and characterize the effects of those variables. Another is to learn the mechanisms by which LCPUFA status may influence behavior.