Mupirocin (MUP), a potent antibacterial agent, has been a cornerstone of topical antimicrobial therapy for several decades. As an older, yet widely used antibiotic, MUP has exhibited efficacy against various bacterial strains, making it a versatile tool in the management of a range of infections. The review synthesizes available literature to highlight the evolution of MUP, from its initial discovery to its current status as a go-to topical antibiotic. In the era of rising antibiotic resistance, MUP is positioned as a valuable therapeutic option due to its broad-spectrum activity against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Emphasis is placed on its distinctive role in different infections, enhanced efficacy with different additives, and newer drug delivery strategies.In addition to its classical applications in impetigo and other superficial skin infections, this review delves into emerging indications and novel uses of MUP, potentially expanding its clinical utility. The exploration of combination therapies, alternative formulations, and ongoing research endeavors will contribute to a forward-looking perspective on the role of MUP in future antimicrobial strategies.