AbstractNaegleria fowleri, a thermophilic flagellate amoeba known as a “brain‐eating” amoeba, is the aetiological agent of a perilous and devastating waterborne disease known as primary amoebic meningoencephalitis (PAM), both in humans as well as in animals. PAM is a rare but fatal disease affecting young adults all around the world, particularly in the developed world but recently reported from developing countries, with 95%–99% mortality rate. Swimmers and divers are at high risk of PAM as the warm water is the most propitious environment adapted by N. fowleri to cause this infection. Infective amoeba in the trophozoite phase enter the victim's body through the nose, crossing the cribriform plate to reach the human brain and cause severe destruction of the central nervous system (CNS). The brain damage leads to brain haemorrhage and death occurs within 3–7 days in undiagnosed cases and maltreated cases. Though the exact pathogenesis of N. fowleri is still not known, it has exhibited two primary mechanisms, contact‐independent (brain damage through different proteins) and contact‐dependent (brain damage through surface structures food cups), that predominantly contribute to the pathogen invading the host CNS. For the management of this life‐threatening infection different treatment regimens have been applied but still the survival rate is only 5% which is ascribed to its misdiagnosis, as the PAM symptoms closely resembled bacterial meningitis. The main objectives of this review article are to compile data to explore the sources and routes of N. fowleri infection, its association in causing PAM along with its pathophysiology; latest techniques used for accurate diagnosis, management options along with challenges for Pakistan to control this drastic disorder.