Staphylococcus aureus (S. aureus) infections, especially methicillin resistant (MRSA), constitute an alarming public health issue due to its association with high mortality, morbidity, and hospitalization costs. The increasing antibiotic resistance and biofilm-associated infections of MRSA prompted the discovery of novel and more effective therapeutic strategies. Our team has been working on alternative therapies against S. aureus infections. For this, we have been repurposing an existing antibacterial drug, rifabutin (RFB), through its association to a nanotechnological platform, liposomes, aiming to promote a preferential targeting to infected sites and maximizing its potential antibacterial effect. The therapeutic potential of RFB formulations against a MRSA commercial strain (MRSA ATCC®-33592), either in planktonic or biofilm forms, was assessed. RFB displayed higher antibacterial effects towards biofilm than vancomycin (VCM), the gold standard treatment against MRSA infections, with MBIC