The fields of synthetic biology and microbiome research have expanded greatly over the last decade enabling the development of new therapeutic strategies using engineered microbes that operate from within the gut. Synlogic is pioneering the development of a novel class of engineered, living drugs, called Synthetic Biotic™ Medicines, that can be designed to correct missing or dysfunctional metabolic activities or deliver effectors in the GI tract, with the potential to treat a wide range of diseases. The opportunities and challenges of this new therapeutic platform and the results obtained with two lead programs for the treatment of Urea Cycle Disorder and Phenylketonuria will be presented.