Staphylococcus aureus is an opportunistic gram-positive pathogen responsible for a wide variety of animal and human infections. In humans, it is associated with both superficial and invasive cases of infections, including bacteremia, endocarditis, osteomyelitis, septic arthritis, keratinitis, pneumonia and catheter-related infections. The prevalence of S. aureus as a human pathogen has been attributed to its ability to form specific bonds with a wide variety of extracellular matrix (ECM) proteins. These binding events contribute significantly to the molecular mechanisms of S. aureus virulence. Additional virulence properties incur from its capacity to colonize surfaces in organized biofilm communities and from the occurrence of secondary metastatic infections caused by bacterial cells detaching from biofilms growing under shear stress. Microbial biofilms have also been associated with the spread of community-acquired bacterial infections and the emergence of resistant bacterial variants. The treatment of biofilm-associated infections costs over $1 billion annually in the United States. As a result, the study and characterization of microbial biofilms is rapidly gaining interest in the scientific community. The overall ambition of this project was to investigate the effects of physiologically relevant hydrodynamic forces on the accumulation and proliferation of S. aureus biofilms onto biotic substrates. Additionally, we evaluated the ability of sodium metaperiodate to inhibit the growth of S. aureus biofilms in vitro under both static and dynamic conditions. In the course of these studies, we demonstrated that: (1) hydrodynamic forces and nutrient availability modulate the rate of growth and the internal structure of early S. aureus biofilms grown on biotic surfaces; (2) through the process of erosion, S. aureus biofilms grown under physiologically relevant hydrodynamic conditions release planktonic cells with reduced adhesion avidity to ECM proteins; (3) these eroded planktonic cells demonstrate the potential to initiate secondary biofilm formations; and (4) under hydrodynamic conditions, S. aureus biofilms can withstand antimicrobial challenges that would otherwise be detrimental to sessile cultures grown under static conditions and to individual cells grown in suspension. The current research extended our understanding of the physiological effects of fluid shear forces on the development of S. aureus biofilms. It is essential to establish the principal factors leading to the multilayered accumulation of staphylococcal biofilms in vivo in order to design alternative therapeutic approaches to treating S. aureus infections.