AbstractBacterial resistance toward broad‐spectrum antibiotics has become a major concern in recent years. The threat posed by the infectious bacteria and the pace with which resistance determinants are transmitted needs to be deciphered. Soil and water contain unique and diverse microbial communities as well as pools of naturally occurring antibiotics resistant genes. Overuse of antibiotics along with poor sanitary practices expose these indigenous microbial communities to antibiotic resistance genes from other bacteria and accelerate the process of acquisition and dissemination. Clinical settings, where most antibiotics are prescribed, are hypothesized to serve as a major hotspot. The predisposition of the surrounding environments to a pool of antibiotic‐resistant bacteria facilitates rapid antibiotic resistance among the indigenous microbiota in the soil, water, and clinical environments via horizontal gene transfer. This provides favorable conditions for the development of more multidrug‐resistant pathogens. Limitations in detecting gene transfer mechanisms have likely left us underestimating the role played by the surrounding environmental hotspots in the emergence of multidrug‐resistant bacteria. This review aims to identify the major drivers responsible for the spread of antibiotic resistance and hotspots responsible for the acquisition of antibiotic resistance genes.