Acanthamoeba infection, a ubiquitous amoeba found in various environments, can pose a threat to human health, causing infections with diverse clinical presentations. In addition to the well-documented Acanthamoeba keratitis, where the amoeba invades the cornea, Acanthamoeba can also cause chronic granulomatous amebic encephalitis (GAE) primarily affecting immunocompromised individuals. GAE progresses slowly, leading to neurological symptoms such as headache, altered mental status, and seizures. Acanthamoeba infections are notoriously challenging to diagnose, often requiring specialized tests such as molecular assays or brain biopsy for GAE. Treatment involves a combination of antimicrobial agents, including drugs like pentamidine and flucytosine. The prognosis remains guarded, especially in cases of GAE, highlighting the importance of early detection and aggressive intervention. Preventive measures involve practicing good hygiene, particularly in contact lens use, as improper lens care is a major risk factor for Acanthamoeba keratitis. Increased awareness among healthcare professionals and the public is crucial to recognizing and addressing Acanthamoeba infections effectively, given their potential for severe and life-threatening outcomes. Ongoing research aims to improve diagnostic tools and therapeutic strategies for these complex and often challenging-to-treat infections.