<p>Engineered cell therapies are transforming precision medicine by enabling real-time, context-responsive interventions that act upon disease-specific cues. Inspired by the success of CAR-T cells in oncology, next-generation platforms are being developed using diverse immune cells and stem cells to address a broader spectrum of diseases. These living therapeutics harness synthetic gene circuits to induce targeted cytotoxicity, to modulate the secretion of effector proteins or to coordinate both functions in response to endogenous signals or externally delivered molecular and physical triggers. Ex vivo engineering of autologous cells remains the norm, but challenges in scalability, cost and accessibility are fuelling efforts towards allogeneic products and in vivo reprogramming. Advances in targeted delivery — using viral vectors, mRNA-loaded nanoparticles and virus-like particles — are expanding the toolkit for direct programming of cells within the body. This Review discusses emerging strategies for engineering human cells with therapeutic functions, highlighting modular control systems, delivery innovations and the translational hurdles that lie ahead.</p>