The emergence and alarming increase of multiresistant strains of Staphylococcus aureus emphasizes the need for new and inovative antimicrobial strategies. One of them is phage therapy that represents a promising alternative to the use of antibiotics for combating bacterial infections. Some strains, however, are resistant to therapeutic bacteriophages, which may decrease the effectivity of phage-based drugs. In our study, we analyzed causes responsible for this resistance, mainly: (i) efficacy of phage adsorption to bacterial cells; (ii) interference with the products of the prophage-borne genes in lysogenic strains; and (iii) effect of CRISPR-Cas elements.