Autoimmune encephalitis (AIE) represents a category of relatively newly described neurological disorders associated with an increasing prevalence, a significant impact on the healthcare system, and a high rate of intensive care unit (ICU) admission. This category of diseases often requires prompt treatment, even before a definitive diagnosis is established. In the ICU, patients present with nonspecific signs and symptoms for AIE, which pose challenges in both management and diagnosis. Patients frequently exhibit dysautonomia, severe physical and psychic agitation, as well as tremors and dyskinesia, all of which complicate the diagnosis. They are prone to developing infections, including ventilator-associated pneumonia, and issues related to difficult venous access and pressure ulcers. Early initiation of immunosuppressive treatment is necessary to improve patients’ outcome. Through this article, we aimed to summarize current knowledge in terms of the difficulties in diagnosing and management of this pathology in the ICU, as well as the implications for the healthcare system in terms of human and financial resources.