Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered a respiratory pathogen, myriad neurologic complications—including confusion, stroke, and neuromuscular disorders—manifest during acute COVID-19. Furthermore, maladies such as impaired concentration, headache, sensory disturbances, depression, and even psychosis may persist for months after infection, as part of a constellation of symptoms now called Long Covid. Even young people with mild initial disease can develop acute COVID-19 and Long Covid neuropsychiatric syndromes. The pathophysiological mechanisms are not well understood, although evidence primarily implicates immune dysfunction, including nonspecific neuroinflammation and antineural autoimmune dysregulation. It is uncertain whether unforeseen neurological consequences may develop years after initial infection. With millions of individuals affected, nervous system complications pose public health challenges for rehabilitation and recovery and for disruptions in the workforce due to loss of functional capacity. There is an urgent need to understand the pathophysiology of these disorders and develop disease-modifying therapies.