Development of novel antibiotics requires a deeper understanding of the host-immune system and individual-level differences in the host immune system are responsible for differential results of the same antibiotic treatment in any population. While traditional antibiotic approaches continue to be utilized for treatment of bacterial infections, the biggest challenge remains the development and persistence of antimicrobial resistance. Bacteria are either naturally resistant to some antibiotics, or they develop antibiotic resistance through gene transfer. The problem is compounded by the fact, that the development of antimicrobial resistance in bacterial species is much faster than the pace of development of any novel antibiotic. Moreover, the development of antibiotics is more challenging for Gram-negative bacteria as they have an outer membrane which prevents the entry of various drugs. Another major challenge is the treatment of bacterial infections if the bacteria form biofilms as biofilms prevent the entry of antibiotics and the lowest concentration of antibiotics entering the biofilm can promote the development of antimicrobial resistance. Therefore, there is a dire need for novel antibacterial materials such as peptides, bacteriophages, enzymes, biopolymeric materials, and hydrogels that can help mitigate the issues with currently available antibacterial drugs. Another major advancement is the use of artificial intelligence (AI) and machine learning (ML) based approaches, CRISPR-based gene editing methodologies, that have slowly started entering the field of antibiotics which can significantly reduce the timeline for the development of any new antibiotic. The widespread use of AI is still in the nascent stages, and it requires more research efforts in the future. A better understanding of resistance in bacteria can help in the development of novel antibiotics and treatment strategies to manage bacterial infection.