Since penicillin was discovered by Sir Alexander Fleming in 1928, antibiotics have been used in medicine to treat different infections to combat pathogenic microorganisms. Nevertheless, with their increasing and massive use, progress of resistance has become more predominant and many bacteria have developed resistance to multiple classes of antibacterial agents through genetic exchange mechanisms. Consequently, the use of antibiotics is now under threat. Antibiotic resistance poses a worldwide hazard to both human and animal health and it has become an important public health concern in the 21st century. This review aims to survey some mechanisms of antibiotic resistance. Furthermore, some novel approaches like the use of nanoparticle-based antimicrobial drug delivery, fecal microbiota transfer, antimicrobial peptides, antibiotic adjuvants, antisense antimicrobials, phage therapy, antivirulence strategies, host oriented therapy, synthesis of new antimicrobials and extraction of antimicrobials from natural source like plants are identified and discussed in an attempt to combat and fight against bacterial resistance.