Climate change and food security are two of our most significant global challenges of our time. Conventional approaches for food production not only produce greenhouse gases but also require extensive land and water resources. An alternative is to use gas fermentation to convert greenhouse gases as feedstocks into microbial protein-rich biomass (single-cell protein). Aerobic methanotrophic (methane-oxidising) and hydrogenotrophic (hydrogen-oxidising) bacteria, which produce biomass using gases as their energy and carbon sources, are ideal candidates for single-cell protein production. However, multiple innovations are required for single-cell protein production to be economical and sustainable. Although current technologies rely on conversion of purified single gaseous substrates, the potential to directly use mixed gas streams from point sources remains reasonably unexplored. In addition, there is much potential to increase nutritional and commercial value of single-cell protein through synthetic biology. In this perspective, we discuss the principles, approaches, and outlook for gas fermentation technologies aiming to significantly reduce greenhouse gas emissions and enhance food security.