Unpressurized aircraft routinely operate at altitudes where hypoxia may be of concern. A systematic literature review was conducted regarding hypoxic impairment, including mental functions, sensory deficits, and other pertinent research findings that may affect aviation-related duties at moderate altitude (8000 to 15,000 ft/2438 to 4572 m). The results of this review suggest that cognitive and psychomotor deficits may include learning, reaction time, decision-making, and certain types of memory. However, results are difficult to quantify and reliably reproduce. Inconsistency of results may be related to the subtlety of deficits compared to high altitude, differences among individual compensatory mechanisms, variation in methodology or sensitivity of metrics, presence or absence of exercise, heterogeneous neuronal central nervous system (CNS) response, and interindividual variation. Literature regarding hypoxic visual decrements is more consistent. Rod photoreceptors are more susceptible to hypoxia; visual degradation has been demonstrated at 4000 to 5000 ft (1219 to 1524 m) under scotopic and 10,000 ft (3048 m) under photopic conditions. Augmented night vision goggle resolution demonstrates more resilience to mild hypoxic effects than the unaided eye under starlight conditions. Hypocapnia enhances visual sensitivity and contrast discrimination. Hyperventilation with resulting respiratory alkalosis and cerebral vasoconstriction may confound both cognitive/ psychomotor and visual experimental results. Future research should include augmentation of validated neuropsychological metrics (surrogate investigational end points) with actual flight metrics, investigation of mixed gas formulations, contribution of hypocapnic vasoconstrictive effects on hypoxic performance, and further investigation into cellular- and systems-level approaches for heterogeneous CNS response. Research is also required into the contribution of mild-moderate hypoxia in human factors- and spatial disorientation-related mishaps.