Case histories are presented of 2 individuals (a 5-year-old girl and 64-year-old man) who developed encephalitis caused by the free-living amoeba Balamuthia mandrillaris. Both individuals survived after diagnosis and initiation of effective antimicrobial therapy. Immunostaining for Balamuthia-specific antibody levels identified the causative agent of the infections. Antimicrobial therapy with flucytosine, pentamidine, fluconazole, sulfadiazine, and a macrolide antibiotic (azithromycin or clarithromycin) was initiated. Phenothiazines (thioridazine and trifluoperazine) were also used. Both patients recovered, and there was no evidence of recrudescence of the disease at 2 and 6 years after onset of symptoms. Awareness of Balamuthia as the causative agent of encephalitis and early initiation of antimicrobial therapy were critical to the recovery of both patients. Although optimal antimicrobial therapy for Balamuthia amoebic encephalitis has yet to be determined, the antimicrobials used in these 2 cases effectively controlled the disease. These 2 individuals are the only known survivors of this otherwise fatal type of amoebic encephalitis.