Staphylococcus aureus is a major human pathogen that causes a wide variety of different diseases due to the fact that it can adopt a range of different growth states and lifestyles, including growing as biofilms. Additionally S. aureus infections can be complicated by the fact that it can develop resistance to antibiotics, which is a growing worldwide problem. In vivo models of disease can provide us with deeper understanding of infection dynamics and how pathogens respond to existing antibiotics, as well as screening new treatments. Here, I use the zebrafish embryo model of S. aureus infection and fluorescence microscopy to explore how S. aureus responds to antibiotic treatment in conjunction with the innate immune system, as well as how biofilms form in vivo. I have found that S. aureus responds differentially to the antibiotics tetracycline and oxacillin, and using spinning disk microscopy was able to show that oxacillin is able to shrink abscesses in zebrafish embryos. Using in vitro methods, I have demonstrated that combining oxacillin with tetracycline has a bacteriostatic effect, despite the fact that oxacillin alone is bactericidal. Interestingly, when the antibiotics are used in combination, they display synergy in the zebrafish model. Additionally, the combination can control infection in embryos with depleted phagocytes, thereby preventing growth of S. aureus. Using spinning disk microscopy I have visualised expression of the biofilm related genes nuc and lrgAB in relation to macrophages and neutrophils, and shown that expression is variable through the course of infection. This work has established how combining oxacillin and tetracycline has the potential to be an effective therapy for S. aureus and provides insight into the role the innate immune system has to play alongside antibiotic treatments.