Social interaction among cells is essential for multicellular complexity. But how do molecular networks within individual cells confer the ability to interact? And how do those same networks evolve from the evolutionary conflict between individual- and population-level interests? Recent studies have dissected social interaction at the molecular level by analyzing both synthetic and natural microbial populations. These studies shed new light on the role of population structure for the evolution of cooperative interactions and revealed novel molecular mechanisms that stabilize cooperation among cells. New understanding of populations is changing our view of microbial processes, such as pathogenesis and antibiotic resistance, and suggests new ways to fight infection by exploiting social interaction. The study of social interaction is also challenging established paradigms in cancer evolution and immune system dynamics. Finding similar patterns in such diverse systems suggests that the same ‘social interaction motifs’ may be general to many cell populations.