Promising many societal benefits, emergent products of biotechnology involve releasing genetically modified microbes (GMMs) into the environment. However, regulatory challenges limit their use. So far, GMMs have mainly been tested in agriculture and environmental cleanup, with few approved for commercial purposes. Current government regulations inadequately address modern genetic engineering and limit the potential of gut therapeutics, skin products, self-repairing materials, ocean pollution treatment, anti-corrosion coatings, etc. This review first describes current U.S. regulations for engineered bacterial release. We analyze 57 global studies on soil-released GMMs and laboratory microcosm experiments. We discuss the environmental behavior of released bacteria and offer engineering guidelines to improve performance, control persistence, and reduce risk. Advanced technologies that improve GMM function and control, but lead to increases regulatory scrutiny, are reviewed. Finally, we propose a new regulatory framework informed by recent data to maximize the benefits of GMMs and rapidly address risks.