The rapid rise of antibiotic resistance among infectious pathogens is a matter of grave concern. This development of resistance is an evolutionary process, which is intensified due to prolonged and excessive exposure to antibiotics, which will ultimately force us to a situation where well-established lines of treatment will cease to be effective against routine infections. Thus, it is imperative to develop novel strategies to tackle this silent pandemic of antibiotic resistance. Here we briefly summarize the far-reaching implications of antibiotic resistance globally and highlight some key mechanisms by which resistance arises. We also discuss possible approaches to address this problem, including the identification and validation of novel antibacterial pathways that can circumvent existing resistance mechanisms to effectively curb this global threat.