Sleep apnea is an important cause in sleep medicine for a direct sustained assault on the brain, and also indirectly through a range of mechanisms. This chapter summarizes some of these mechanisms, as they are all active in the obstructive sleep apnea (OSA) patient. Sleep deprivation/fragmentation, and sleep apnea, alters task-related activation in the executive network. Brain-derived neurotrophic factor (BDNF) may be a special link between sleep, cognition, and brain health. Supportive evidence of a central role for BDNF in sleep homeostasis has emerged, particularly providing a link between wake and use-dependent synaptic plasticity and subsequent slow-wave sleep. Structural and functional imaging can establish if genomic modifiers such as these modify the impact of sleep hypoxia or sleep fragmentation on the adult or pediatric brain structure and function, including cognition. Such imaging genomics has shown some utility in assessing the effects of stimulants in relation to catecholamine metabolizing pathway polymorphisms.