Acanthamoeba is a free-living amoeba that is widely distributed in the environment. It is an opportunist protist, which is known to cause rare yet fatal infection of the central nervous system (CNS), granulomatous amebic encephalitis (GAE) in humans. GAE cases are increasingly been reported among immunocompromised patients, with few cases in immunocompetent hosts. Diagnosis of GAE primarily includes neuroimaging, microscopy, cerebrospinal fluid (CSF) culture, histopathology, serology and molecular techniques. Early diagnosis is vital for proper management of infected patients. Combination therapeutic approach has been tried in various GAE cases reported worldwide. We tried to present a comprehensive review, which summarizes on the epidemiology of GAE caused by Acanthamoeba along with the associated clinical symptoms, risk factors, diagnosis and treatment of GAE among infected patients. •Updates on epidemiology, diagnosis and treatment of Acanthamoeba causing GAE among infected patients.•Acanthamoeba-endosymbionts relationship.•Tabular presentation of GAE cases caused by Acanthamoeba worldwide during 1990–2018.•Worldwide distribution of cases reported during 1990–2018.