Accurate identification of nervous system dysfunction is vital in the assessment of any multisystem disorder. The neurologic manifestations of acid-base disturbances, abnormal electrolyte concentrations, and acute endocrinopathies are protean and typically determined by the acuity of the underlying derangement. Detailed history and physical examination may guide appropriate laboratory testing and lead to prompt and accurate diagnosis. Neurologic manifestations of primary and secondary systemic disorders are frequently encountered in all subspecialties of medicine. This article focuses on key neurologic presentations of respiratory and metabolic acid-base derangements and potentially life-threatening endocrinopathies.