The development and approval of new antimicrobials capable of being used to treat infections caused by multidrug-resistant pathogens has not kept pace with the rapid emergence of bacterial resistance. Without a doubt, there is a critical unmet need for the identification of novel strategies to develop antimicrobials to deal with this new scourge. One strategy, which warrants special attention as a unique method for identifying new antimicrobials, is drug repurposing. Several approved drugs have been successfully repurposed for different ailments giving hope that this strategy can also be utilized to uncover new antibacterials. To aid in this process, the present review presents non-antimicrobial approved drugs and clinical molecules, which have been shown to possess antimicrobial activity against Staphylococcus aureus and their potential clinical applications. Additionally, approved drugs with novel applications such as interference in staphylococcal pathogenesis and host immunomodulators are also explained. The current review also discusses the challenges associated with repurposing already approved non-antimicrobial drugs as antibacterials and potential uses of these drugs that can be further explored in order to develop novel therapeutics for the treatment of multidrug- resistant staphylococcal infections. Collectively, the information presented demonstrates that repurposing approved drugs and clinical molecules as antimicrobials may help to speed up the drug development process and save years of expensive research invested in antimicrobial drug development.