Nature Reviews Bioengineering, Published online: 24 August 2026; doi:10.1038/s44222-026-00470-2Multicellular assemblies can be programmed to exhibit emergent behaviours that make them promising therapeutic tools, particularly for tissue regeneration and immunomodulation. This Review outlines the design principles, biological advantages and translational requirements for engineering hierarchical cellular assemblies with programmable functions and emphasizes the need for benchmarking them against single-cell and biomaterial-based approaches.