In the immature brain, GABA (γ-aminobutyric acid) is an excitatory neurotransmitter. With development, GABA becomes inhibitory due to the changes in the expression level of chloride transporters, leading to a negative shift in chloride ions. Clinical evidence and studies in animal models indicate greater brain damage in male versus female neonates following a variety of neuronal insults. The recent finding of Nunez and McCarthy suggest a mechanism whereby androgens may endanger male neurons to the possible excitotoxic effects of excitatory GABA in neonates. Given our growing understanding of the excitatory immature GABAergic system and how sex, age and hormone milieu can influence this system, such studies might pave a path for novel clinical treatments to alleviate neonatal risk for brain injury.