Microbial infections have been the leading cause of death throughout history. This was changed when antibiotics were discovered, causing an increase in life expectancy from 48 years to 72 years. However, this golden era might end very soon. Bacteria have evolved resistance against antibiotics using different pathways. Therefore, restrictive policies about using antibiotics should be implemented by the healthcare system to prevent the further spread of bacterial resistance. However, these policies might not be enough without discovering or synthesizing new antibiotics. Antibiotics synthesis or discovery is a lengthy, tedious multistage process. Moreover, the development of bacterial resistance against any newly developed antibiotics takes around 10 years. Therefore, there is a need to find another strategy to retain the current available antibiotics activity against micro-organisms. Nanotechnology is a cutting-edge science that has been emerged few decades ago, it is concerned with producing fibers or particles in the nanometer scale. In literatures, nanoparticles were shown to improve the drug solubility, bioavailability, modify drug pharmacokinetics, increase drug stability, target drug into certain sites and moreover, were proven to overcome some developed resistance mechanisms against anticancer drug (e.g. Efflux mechanism). Recently, nanotechnology techniques have been applied to combat microbial infections and they were proven to be able to overcome the bacterial developing resistance mechanism.  In this review, we are presenting a historical background of antibiotics and discussing some bacterial developed resistance mechanisms as well as stating different nano-based formulations that were developed and proved to be effectively potentiate the antibiotic activity against some resistant micro-organisms.