It is a very serious global health issue as it reduces the effectiveness of antibacterial drugs and also makes the treatment of infectious diseases quite challenging. Thus, this review highlights complex factors of antibiotic resistance that include the misuse and overuse of antibiotics both in health and agriculture sectors while reporting genetic mechanisms through which resistance develops. Several major antibiotic-resistant pathogens already identified include multidrug-resistant tuberculosis, methicillin-resistant Staphylococcus aureus, and carbapenem-resistant Enterobacteriaceae. These are the greatest public health threats, thus it is a great move to discuss some of these current approaches that will in turn help combat this crisis of antibiotic resistance including stewardship programs, developing new antimicrobials, as well as prevention through vaccinations. We further discuss the role of international health organizations, especially the World Health Organization, in coordinating efforts across the globe to contain the increasing menace of antimicrobial resistance through surveillance, research, and cooperative actions. Finally, we introduce new approaches which may change the face of the future of antibiotic resistance management: phage therapy, CRISPR technology, and use of antimicrobial peptides. This is a big step forward toward the goal but leaves many serious challenges open for the door: economic and regulatory ones related to developing new antibiotics, access imbalances concerning medications, and public knowledge and awareness lacunas. Ultimately, comprehensive, multi-institutional collaboration is what will get this job done: ensure antibiotics continue working well and continue protecting public health.