Aerotoxic syndrome is a rarely recognized and poorly defined illness resulting from exposure to products of oil combustion in commercial aircraft bleed air systems. The pathophysiology of this syndrome is not well understood. A 42-year-old male pilot developed duty-limiting symptoms consistent with aerotoxic syndrome following exposure to airline cabin fumes and recurrence of symptoms following re-exposure despite apparent full recovery from the initial exposure event. Given his persistent symptoms and concern for immediate debilitation/incapacitation if re-exposed, the pilot was deemed medically unqualified for return to commercial piloting duties and a disability determination was made. Consideration of aerotoxic syndrome in aircrew members with unusual or episodic symptoms of neuro/cognitive dysfunction is essential for further characterizing this occupational illness, guiding medical management, and understanding its impact on aviation workforce health.