Bacteria sense and respond to the environment, communicate, and continuously interact with their surroundings, including host bodies. For more than a century, engineers have been trying to harness the natural ability of bacteria as live biotherapeutics for the treatment of diseases. Recent advances in synthetic biology facilitate the enlargement of the repertoire of genetic parts, tools, and devices that serve as a framework for biotherapy. This review describes bacterial species developed for specific diseases shown in in vitro studies and clinical stages. Here, we focus on drug delivery by programing bacteria and discuss the challenges for safety and improvement.