Objective: The authors described clinical presentations of oral and genital herpes simplex virus (HSV) infections in a university health population and implications of these findings. Participants and Methods: Using a standardized data collection tool, 215 records of patients with symptomatic culture-positive HSV infections were reviewed. Results: HSV-1 accounted for 78% of female and 85% of male genital herpes (GH) infections, and oral herpes (OH) infections presented as an acute febrile illness (AFI) in 51% of those 18 to 24 years old. HSV-2 accounted for 68% of GH infections among adults 25 or older. Conclusions: As seroprevalence for both HSV-1 and HSV-2 in the United States is decreasing, a growing college age cohort is at risk for primary HSV-1 infection. The proportion of GH caused by HSV-1 also continues to increase. This understanding has implications for clinical care, sexual health programming, and counseling strategies. (Contains 2 tables and 1 figure.)