Two-dimensional topological insulators (2D TIs) are a remarkable class of atomically thin layered materials that exhibit unique symmetry-protected helical metallic edge states with an insulating interior. Recent years have seen a tremendous surge in research of this intriguing new state of quantum matter. In this Perspective, we summarize major milestones and the most significant progress in the latest developments of material discovery and property characterization in 2D TI research. We categorize the large number and rich variety of theoretically proposed 2D TIs based on the distinct mechanisms of topological phase transitions, and we systematically analyze and compare their structural, chemical, and physical characteristics. We assess the current status and challenges of experimental synthesis and potential device applications of 2D TIs and discuss prospects of exciting new opportunities for future research and development of this fascinating class of materials.