As a quintessential “One Health” issue, antimicrobial resistance (AMR) can be transmitted in the environment via multiple pathways, thereby constituting an integral dimension of the human-animal-environment loop. Only recently has air been recognized as a potentially important pathway for the dissemination of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria. This review presents the current know-how about the hypothesized dissemination from emission sources to human airways in association with influencing environmental factors and the consequent health implications. The presence of ARGs in source-specific and ambient air is no longer in question. The transport propensity of antibiotic-resistant bacteria needs to be quantified in order to assess the magnitude of the inhalation exposure of occupational and general populations. Reactive atmospheric components and prevailing meteorological conditions strongly influence the dynamics of and exposure to ambient inhalable ARGs. Considering the evolving trends of air pollution and climate change, such impacts on antibiotic-resistant pathogens need to be systematically studied. The ultimate question is the fate and consequences of inhalable AMR in interaction with microbiomes in healthy and diseased human airways, which would shed light on the role of AMR in viral-bacterial co-infections leading to acute and chronic respiratory diseases. We put forward a holistic methodological framework to address the major research gaps to establish the airborne transmission chain of antimicrobial resistance. An advanced understanding of these issues will be of benefit in devising effective control and management measures to minimize the airborne transmission of AMR, an integral environmental dimension to protecting the health of large populations. Graphical abstract