Throughout history, human life has been seriously threatened by bacterial infectious diseases. After the discovery of antibiotics, humanity thought it had won the fight against infectious bacteria. However, considering the rapid evolution of bacterial multidrug resistance and exhausted pipeline of antibiotics for fighting bacterial infectious diseases, we are approaching the ‘post-antibiotic’ era. Unlike eukaryote, bacteria are proficient in exchanging their genetic materials with others by means of horizontal gene transfer (HGT). As a vehicle for antibiotic resistance gene (ARG), plasmid is self-replicable and transferable in a wide range of host bacteria. Moreover, ways of HGT-mediated ARGs spreading are highly diverse among different species, implicating complex evolution routes for the development of multidrug resistance in bacteria. In recent years, multidrug resistance plasmids have been widely found in bacteria not only from clinical patients, but also from animals, birds and plants, as well as from natural environmental settings including soil and water – heralding that the ‘post-antibiotic’ era is much closer than we previously thought. The global crisis of multidrug resistance calls for a closer collaboration among people of different professions in different regions, countries and continents, which will help us recognize the current situation and eventually find effective and long-lasting solutions for fighting against infectious bacteria.