It is clear from animal studies that commonly used anesthetic agents affect early brain development both histologically and functionally. With human epidemiologic evidence suggesting an association between anesthesia and surgery early in life and late-onset learning disabilities, investigators have focused their attention on the subtle long-term effects of anesthesia exposure. Most obstetric anesthesia studies, however, have focused on either the teratogenic effects of anesthetic agents in the first trimester or on the neonatal status immediately after delivery. Not much attention has been paid to the human second trimester, a period of active fetal brain development typified by neurogenesis and neuronal migration. Of concern though, is that these events are easily perturbed by environmental and pharmacological influences. New research studies have raised significant questions about the fetal impact of maternal anesthesia for non-obstetric and fetal surgery. This review summarizes the major findings in the field of developmental neurotoxicity of anesthetic agents, discusses the susceptibility of the fetal brain to anesthetic effects in a trimester-specific style, and outlines the pitfalls in extrapolating animal research to humans.