Acute or sub acute, generalized or focal encephalopathy characterized by seizures, confusion, mental deterioration or psychiatric symptoms has been associated with antibodies against nervous system or other antigens such as anti-thyroid or anti-aquaporin-4 (neuromyelitis optica or NMO) antibodies. In addition, novel antibodies against molecules or receptors of the central nervous system such as N-methyl d-aspartate receptor (NMDAR), voltage gated potassium channel (VGKC) and glutamic acid decarboxylase (GAD) have been identified in behavioral, epileptic, or movement disorders of sub acute onset in children. Dyskinesias, sleep disturbances, autonomic symptoms and ataxia can also be part of the clinical picture. MR imaging, EEG and cerebrospinal fluid analysis may point to cerebral parenchymal inflammation, or can be normal. In children, these entities are often non-paraneoplastic. Acute severe epilepsy with a febrile onset and acquired partial epilepsy syndromes, some collected under specific acronyms, have also been associated with an antibody-mediated encephalopathy. All these relatively recently described syndromes require a large index of suspicion and early initiation of immunomodulatory treatment. This group of disorders should be considered in all children with unexplained acute or sub acute central nervous system symptoms.