The social insects live in extraordinarily complex and cohesive societies, where many individuals sacrifice their personal reproduction to become helpers in the colony. Identifying adaptive molecular changes involved in eusocial evolution in insects is important for understanding the mechanisms underlying transitions from solitary to social living, as well as the maintenance and elaboration of social life. Here, we review recent advances made in this area of research in several insect groups: the ants, bees, wasps, and termites. Drawing from whole-genome comparisons, candidate gene approaches, and a genome-scale comparative analysis of protein-coding sequence, we highlight novel insights gained for five major biological processes: chemical signaling, brain development and function, immunity, reproduction, and metabolism and nutrition. Lastly, we make comparisons across these diverse approaches and social insect lineages and discuss potential common themes of eusocial evolution, as well as challenges and prospects for future research in the field.