Microbes, amenable to genetic manipulation and capable of rapid growth and multiplication, have found applications in industry, health, agriculture, and the environment. With the emergence of modern biotechnology tools, the exploration of microbes for new applications is indisputable. However, safety concerns abound necessitating regulatory frameworks to guide the manipulation of microbes, their use in manufacturing, processing, treatment and storage of products. These frameworks also extended to metabolites or byproducts of microbes, such as enzymes, proteins, and toxins. Several countries and regions around the world have regulatory frameworks that evaluate, authorize and certify the application of microbes or their products for various purposes. The regulatory frameworks of most countries, such as those covering food, are broadly aligned with the recommendation of the global legislative framework, the Codex Alimentarius. As biotechnology evolves, there is a need for updated regulatory frameworks and circumspection in drafting laws to avoid regulations that could impede competitiveness and innovation.