Neonatal hypoxic-ischemic brain injury (HIBI) and hypoxic-ischemic encephalopathy (HIE) continue to produce significant morbidity and mortality despite implementation of therapeutic hypothermia (TE) as a standard of care. There is consequently an urgent need for alternative therapeutics. The Rice-Vannucci method is an accepted approach for modelling neonatal HIBI in rodents. These rodent models have facilitated discovery of numerous therapeutic targets and analysis of the structural and functional consequences of modulating activity at these targets. Owing to their key roles in diverse physiological and pathophysiological processes, several such targets are ion channels. 4 promising ion channel targets are highlighted in this mini-review, with a focus on key rodent model-based experiments which have helped identify them as such. These are transient receptor potential (TRP) melastatin (M) 7 (TRPM7) and 2 (TRPM2) channels, ATP- sensitive potassium (KATP) channels, and volumeregulated anion channels (VRACs). These and other foundational experiments create hope that future work in rodent models and beyond will enable development of novel therapeutics to reduce the burden of neonatal HIBI and HIE.