Abstract: Hypoxia imposes significant challenge to brain function. Studies have shown that the motor cortex is particularly vulnerable to hypoxia. Experiments with laboratory rodents after hypoxia exposure have shown increased capillary length and microvessal density at motor cortex. Neuroimaging studies on mountain climbers revealed cerebral atrophy at motor cortex. Recent neuroimaging studies on subjects who went through prolonged hypoxia exposure demonstrated decreased cerebrovascular reactivity at the motor cortex, which relates to their lung function parameters. This chapter will review the impact of hypoxia on the morphometry and functionality of the motor cortex with reference to studies using animal models as well as neuroimaging studies on human subjects.