With the accelerating process of industrialization and urbanization, as well as the increasing proportion of the elderly in the world's population, we are facing more complex health threats related to bacterial infection. While the vast majority of the bacteria in the body are rendered harmless by the protective effects of the immune system, the continued abuse and misuse of antibiotics has accelerated the spread of antibiotic-resistant bacterial strains and has resulted in substantial new challenges with respect to modern-day antibiotic-based treatments. Therefore, intelligent design of new antibacterial modalities to be used for treating human and livestock diseases is an extremely urgent priority for researchers in the fields of chemistry, chemical engineering, materials and biomedical sciences. Toward this end, the most intriguing of the new developments are metal-organic frameworks (MOFs). MOFs are versatile crystalline porous lattices of organic ligands and metal ion/clusters that formed by self-assembly via coordination bonds. Due to their unique characteristics, including relatively straight forward and simple methods for synthesis, large surface areas, novel and diverse structures, and adjustable porosity, MOFs not only play strong roles with respect to novel methods for gas storage and separation, they may also be utilized in unique applications associated with sensors mechanisms and catalysis. These features contribute to our current understanding of MOFs as promising candidates for the development of pharmaceutical and specifically antibacterial applications. In this review, antibacterial mechanisms, and the development of resistance to current antibiotic strategies are summarized and discussed. The main mechanisms by which bacteria show resistance to antibiotics include altered metabolic pathways, regulation of target sites, and inactivation, modification, and/or reduction in the capacity to accumulate antibacterial drugs. We consider recent progress on the development of MOFs, including the use of specific metal centers and ligands, metal nanoparticles, and drug-encapsulation, all of which have important applications with respect to antibacterial activities, and wound healing. Finally, the challenges and prospects of MOF-based antibacterial materials are discussed, including critical findings, which will help toward the development of the next generation antibacterial MOFs for human use.