INTRODUCTION: The neurological impact (or lack thereof) of certain medical histories and imaging findings is important to understand in the context of air and spaceflight. There are a number of neurological conditions that, if present in pilots and astronauts, carry variable (and sometimes adverse) functional implications for safety and overall mission success. In this systematic overview, the authors will refer to the relevant clinical and radiological features of brain tumors and vascular anomalies, cerebral edema and intracranial hypertension, concussion and the traumatic brain injury (TBI) spectrum, hematomas, cerebrospinal fluid circulation anomalies including hydrocephalus and sequestrations, spinal degenerative changes, and cerebral ischemia and demyelination. It is notable that these last two conditions have recently been reported to be a complication in some people with coronavirus disease 2019 (COVID-19). A paradigm for practical neurological workup of symptomatic pilots and astronauts will be discussed, as will the controversial notion of pre-emptive radiological screening (vs. not screening) in asymptomatic or clinically occult situations. The concepts of medical surveillance in the setting of known or diagnosed pathologies, and expert panel review and simulator and flight checks in complex neurological cases, are also elaborated on in this paper. We believe this overview will contribute toward the enhancement of a broad understanding of neurological conditions, their clinical workup, and their precautionary management in the setting of aviation and aerospace.Khurana VG, Jithoo R, Barnett M. Aerospace implications of key neurological conditions. Aerosp Med Hum Perform. 2021; 92(2):113119.