In recent years, increased numbers of multidrug-resistant strains of bacteria have opportunistically and selectively expanded while the pharmaceutical discovery of new antimicrobial therapies has been lacking to combat this growing threat. Like traditional antibiotics, botanicals have historically been used to treat bacterial infections, but it remains unclear if bacteria may have the capability to develop resistance to these therapeutic botanicals. It is believed that one advantage that may prevent or slow resistance to botanical antimicrobials is the presumed presence of the multiple endogenous substances contained within a plant that may act synergistically to inhibit microbial growth. This study examined the potential of an antimicrobial-sensitive strain of Staphylococcus aureus to develop resistance to five botanical extracts commonly used for antibacterial therapy. Our results demonstrated that S. aureus was able to develop resistance to the botanical antimicrobial extracts at a similar rate and level as standard antibiotics thus questioning the idea of multiple synergistic antimicrobials within a botanical tincture. These results demonstrate the need for proper use of botanical antimicrobial extracts to avoid the development of resistance to botanical-based therapeutics and avoid similar problems currently faced with pharmaceutical antibiotics.