Longitudinally designed case studies, reporting cognitive and psychosocial outcome of herpes simplex virus encephalitis (HSVE), were conducted prior to current antiviral medication usage and primarily in persons with either left hemispheric or bilateral temporal lobe involvement. The current study demonstrated relatively better outcome (cognitive recovery and functional independence for activities of daily life) in an individual treated with IV Acyclovir within hours of initial symptoms and whose CT scans showed right hemispheric involvement. In contrast with earlier case reports, no semantic specific categories of memory impairment were noted on serial assessment. The time from first symptoms to antiviral medical treatment appears to be the best predictor of outcome from HSVE. Historical case studies with relatively poorer outcome and differing deficits suggest survivors of HSVE are a heterogenous group. Variability in anatomic lesions and time to treatment contribute to outcome.