Since their introduction, the most significant complication of wearing soft contact lenses has been the development of vision-threatening microbial keratitis. In lens-wearing corneas, microbial infection is thought to develop in the absence of overt injury, leading to the hypothesis that microbe interactions with the corneal epithelium are critical to the pathogenesis of this disease. Thus, we have focused our research efforts on understanding microbial virulence mechanisms aimed at corneal epithelial cells and the innate defenses that normally protect them using the gram-negative bacterium Pseudomonas aeruginosa as a model organism. This report summarizes those results and explores their relevance to understanding contact lens-related infections.