A grand challenge in bottom???up synthetic biology is the design and construction of synthetic multicellular systems using nonliving molecular components. Abstracting key features of compartmentalisation, reaction and diffusion, and communi-cation provides the blueprint for assembling synthetic multi -scale systems with emergent properties. The diverse range of chemistries for building encapsulated reactions in micron-sized compartments offers combinatorial flexibility and modularity in building synthetic multicellular systems with molecular-level control. Here, we focus on recent advances in the emerging area of bottom???up approaches to create biologically inspired multicellular systems. Specifically, we consider how intercel-lular communication and feedback loops can be integrated into populations of synthetic cells and summarise recent de-velopments for the 2D/3D spatial localisation of micro -compartments. Although building bottom???up multicellular systems is still in its infancy, progress in this field offers trac-table models to understand the minimal requirements for generating multiscale systems from the molecular level for fundamental research and innovative technological applications.
