Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (CRISPR/Cas) is an acquired immune system developed in evolution of prokaryotes. It provides an immune protection to resist invasion of foreign DNAs or RNAs, such as phages, plasmids and the other mobile genetic elements. CRISPR loci have been identified in genomes of Staphylococcus species. The spacers of the CRISPR arrays usually match with the genes on phages or plasmids derived from the other species or strains of Staphylococcus, and may provide a function to interfere the transmission of exogenous elements related with bacterial virulence, drug resistance and biofilm formation. This review focuses on the unique structure and function of staphylococcal CRISPR/Cas systems.