Naegleria fowleri is the causative agent of primary amoebic meningoencephalitis (PAM) that infects the central nervous system (CNS). The amoeba is present ubiquitously. The infection is rare but has a high mortality rate. The pathogenic amoeba reaches the host through the nasal passage and migrates along the olfactory nerves to reach the human brain and cause severe destruction of the CNS. As Malaysia has a large population that practising ablutions in daily routine, the risk of infection increases. Two mechanisms associated with the infection include contact-dependent and contact-independent. Signs and symptoms vary from early stage to later stage of infection. CSF and brain biopsy are the common specimens collected used to diagnose the PAM infection and usually detect and identify by PCR method. As for treatment, the CDC of United States America has recommended the usage of miltefosine that provides promising in vitro therapy against N. fowleri. This review will discuss more on the occurrence of N. fowleri, pathogenicity, diagnostic tools, and pharmacotherapy approach against N. fowleri infection.