Herpes simplex virus type 1 (HSV-1) is a widespread virus with variable disease severity. HSV-1 is genetically diverse, with certain selective pressures allowing better “fitness” for a viral genotype of interest. Plaque morphology varies between HSV-1 strains, and allows for natural selection to favor certain viral variants in response to dominating selective pressures. Through competition-based experiments, a better understanding of the relationship between HSV-1 genetic variation, fitness, and disease outcome can be established.