Staphylococcus aureus (S. aureus) is the most important gram-positive nosocomial pathogen. Emerging drug resistance among S. aureus isolates is a global concern and the mechanism developed by S. aureus to become resistant to existing antibiotics makes it even more difficult to treat in clinical settings in immunocompromised patients. Efflux pumps are involved in low levels of drug resistance and a combination of drugs with efflux pump inhibitors showed promising reduction in MIC values in many studies. In present studies a series of Chalcones were screened as efflux pump inhibitors and antibiotic modulators in combination with ciprofloxacin using S. aureus strains and the results obtained are promising.