In recent years, synthetic biology has provided many engineering approaches to reprogram and engineer cells in diverse applications including the development of novel therapeutics. Engineered cells provide advantages over small molecules or biologics, as these cells can be reprogrammed to have spatial and temporal control over the delivery of therapeutics in response to disease biomarkers. Herein, some of the recent applications of engineered live bacterial therapeutics against human diseases such as cancer, metabolic disorders, gastrointestinal diseases, and infections are reviewed. Furthermore, this review highlights active clinical trials on engineered cells with promising results.