The atmosphere has been described as one of the last frontiers of biological exploration on Earth. The composition of microbial communities in the atmosphere is still not well-defined, and taxonomic studies of bacterial diversity in the outdoor air have just started to emerge, whereas our knowledge about the functional potential of air microbiota is scant. When in the air, microorganisms can be attached to ambient particles and/or incorporated into water droplets of clouds, fog, and precipitation (i.e., rain, snow, hail). Further, they can be deposited back to earth’s surfaces via dry and wet deposition processes and they can possibly induce an effect on the diversity and function of aquatic and terrestrial ecosystems or impose impacts to human health through microbial pathogens dispersion. In addition to their impact on ecosystem and public health, there are strong indications that air microbes are metabolically active and well adapted to the harsh atmospheric conditions. Furthermore they can affect atmospheric chemistry and physics, with important implications in meteorology and global climate. This review summarizes current knowledge about the ubiquitous presence of microbes in the atmosphere and discusses their ability to survive in the atmospheric environment. The purpose is to evaluate the atmospheric environment as a source of pathogenic or beneficial microbes and to assess the biotechnological opportunities that may offer.