Infective endocarditis remains an illness that carries a significant burden to healthcare resources. In recent times, there has been a shift from Streptococcus sp to Staphylococcus sp as the primary organism of interest. This has significant consequences given the virulence of Staphylococcus and its propensity to form a biofilm, rendering non-surgical therapy ineffective. In addition, antibiotic resistance has affected treatment of this organism. The cohorts at most risk for Staphylococcal endocarditis are the elderly patients with multiple comorbidities. The innovation of transcatheter technologies alongside other cardiac interventions such as implantable devices have contributed to the increased risk attributable to this cohort. We examine the role of the heart team for diagnosis and treatment of this condition. In addition, we examine the determinants of virulence of Staphylococcus aureus, the interaction with hosts immunity and the discovery and emergence of a potential vaccine. We also examine the potential role of prophylactic antibiotics during dental procedures. With increasing rates of transcatheter device implantations, there is a projected increment of endocarditis especially in this high-risk group. A high index of suspicion is needed alongside early initiation of therapy and referral to the heart time to improve outcomes.