Methicillin-resistant Staphylococcus aureus is a leading cause of morbidity and mortality with multiple chronic infections. The proficiency of S. aureus as a pathogen, coupled with its ability to acquire antibiotic resistance, makes it a formidable infectious agent. S. aureus owes a large part of its success as a pathogen to its ability to form robust biofilms that can withstand relatively higher levels of antimicrobials compared to a planktonic or single-celled population of bacteria. Biofilms are organized communities of bacteria encased in a protective matrix often composed of protein, DNA and polysaccharides, and are commonly found during chronic infection. Planktonic and biofilm bacteria grow in distinct metabolic states and therefore exhibit virulence traits that are characteristic to each mode of growth. Most studies to understand the mechanisms of S. aureus pathogenesis have been done with planktonic populations. However, owing to their frequent association with chronic infections, it is of great significance to understand the virulence mechanisms specific to biofilms. The unique virulome of S. aureus biofilms has only recently begun to be understood. The work in this dissertation unravels multiple novel mechanisms of virulence exhibited by S. aureus biofilms that are distinct from planktonic bacteria. This work contributes to our knowledge of S. aureus biofilm virulence and sets a foundation for development of anti-biofilm therapeutic strategies. We show that when grown as biofilms, S. aureus simultaneously utilizes multiple virulence factors to effectively evade being killed by host innate immune cells, specifically neutrophils.