Staphylococcal species are a leading cause of community- and nosocomial-acquired infections, where the placement of foreign materials increases infection risk. Indwelling medical devices and prosthetic implants are targets for staphylococcal cell adherence and biofilm formation. Biofilm products actively suppress proinflammatory microbicidal responses, as evident by macrophage polarization toward an anti-inflammatory phenotype and the recruitment of myeloid-derived suppressor cells. With the rise in prosthetic hip and knee arthroplasty procedures, together with the recalcitrance of biofilm infections to antibiotic therapy, it is imperative to better understand the mechanism of crosstalk between biofilm-associated bacteria and host immune cells. This review describes the current understanding of how staphylococcal biofilms evade immune-mediated clearance to establish persistent infections. The findings described herein may facilitate the identification of novel treatments for these devastating biofilm-mediated infections.