Pediatric inflammatory disorders of the central nervous system are an uncommon but increasingly recognized cause of critical neurological illness.1,2 Despite variation in pathophysiology among these diseases, the typical presentation is that of the acute or subacute onset of neurological deficits with radiographic or laboratory evidence of active CNS inflammation. In many of these diagnoses, early identification and initiation of treatment is essential in the formulation of acute and long-term treatment plans to decrease and prevent further ongoing inflammation. There are varying severities of disease presentation, including those that require ICU level of care. This chapter will review the typical clinical presentations, clinical evaluations and management recommendations for pediatric CNS demyelinating diseases, autoimmune encephalitides, vasculitides, and a few rare disorders with suspected inflammatory etiologies (summarized in Table 1).