Fluoroquinolones are considered one of the widely utilized antibiotics, specifically, with the recent development of newer generations such as moxifloxacin, delafloxacin and finafloxacin which possess a wider spectrum of activity and improved bioavailability. However, alarming increase in bacterial resistance reports worldwide incites medicinal chemists to employ guided-biologically-oriented-synthesis-strategies toward the modulation of quinolones derivatives activity. At present, quinolone scaffold diverse biological activities prompted the fortuitous discovery of novel antimicrobial and anticancer derivatives. Herein, the opponent arguments (2013–2015) regarding the structure activity relationships of fluoroquinolones' antibacterial, anticancer, antifungal activities are inscribed. [ABSTRACT FROM AUTHOR]