Most of the knowledge on Mycoplasma pneumoniae encephalitis in children is based on case reports or small case series. The aim of this study was to assess the important features of the disease by a systematic review of previously published cases. Overall, 58 cases (22 female, 36 male; median age 10 years, range: 2-17 years), derived from 38 reports, were reviewed. Forty-five patients (76%) had flulike or respiratory symptoms prior to the onset of neurologic disease, and 23 patients (40%) presented with pulmonary infiltrates. Cerebrospinal fluid (CSF) pleocytosis (mostly mononuclear cells) and elevated cerebrospinal fluid protein counts were present in 34 (59%) and 21 (36%) patients, respectively. Cranial computed tomography (CT) or magnetic resonance imaging (MRI) abnormalities were seen in 18 (31%) and 17 (29%) patients, respectively, whereby various different presentations were observed. Forty-four patients (76%) received antimicrobial therapy active against mycoplasmas, most frequently erythromycin (n = 29) or minocycline (n = 6). Only in one patient, cure was directly attributed to antimicrobial therapy (with chloramphenicol) by the respective authors. Thirty-three patients (57%) recovered without sequelae, 20 patients (34%) had minor to major sequelae, and 5 patients (9%) died. A high cerebrospinal fluid cell count, cerebrospinal fluid protein elevation, and higher age were associated with an unfavorable outcome.