Staphylococcal infection can cause a wide range of diseases resulting either from staphylococcal bacteria invasion or through toxin production. The majority of infections caused by staphylococci are due to Staphylococcus aureus. Moreover, methicillin-resistant Staphylococcus aureus has recently been considered to be one of the major causes of hospital-acquired infections. The treatment of staphylococci infections is difficult because increased antibiotic resistant strains have become more common, increasing the risk of serious health penalty. Delivery of antibiotics via nanoparticles is a promising therapy, as a drug delivery mechanism, particularly for controlled release or depot delivery of drugs to decrease the number of doses required to achieve a clinical effect. This review emphasized the potential of nanoparticles in the targeted antibiotics for therapy of staphylococcal infections.