The chapter discusses the advancements and applications of synthetic receptors in cell and gene therapies, highlighting their potential to address safety and efficacy concerns. Synthetic receptors, a tool in synthetic biology, can precisely control the function of therapeutic cells and genetic modules by fine-tuning therapeutic activities. The review covers diverse synthetic receptor systems, including chimeric antigen receptors (CARs) and synthetic Notch (synNotch) receptors, and their design, construction, and improvement strategies. It also explores the expanding landscape of therapeutic applications and current challenges in clinical translation. The chapter emphasizes the importance of synthetic receptors in reprogramming therapeutic cells, such as CAR T cells, to enhance their therapeutic effects while minimizing off-target toxicity. Additionally, it discusses the modular nature of synthetic receptors, their ability to sense and respond to various stimuli, and their potential in both biomedical research and clinical treatments.The chapter discusses the advancements and applications of synthetic receptors in cell and gene therapies, highlighting their potential to address safety and efficacy concerns. Synthetic receptors, a tool in synthetic biology, can precisely control the function of therapeutic cells and genetic modules by fine-tuning therapeutic activities. The review covers diverse synthetic receptor systems, including chimeric antigen receptors (CARs) and synthetic Notch (synNotch) receptors, and their design, construction, and improvement strategies. It also explores the expanding landscape of therapeutic applications and current challenges in clinical translation. The chapter emphasizes the importance of synthetic receptors in reprogramming therapeutic cells, such as CAR T cells, to enhance their therapeutic effects while minimizing off-target toxicity. Additionally, it discusses the modular nature of synthetic receptors, their ability to sense and respond to various stimuli, and their potential in both biomedical research and clinical treatments.