Atomic single-molecule imaging has drawn extensive attention for exploring different behaviors and properties of small molecules. However, current techniques still face challenges, due to the thermal activity and beam sensitivity of small molecules. Recently, ångström-level spatial resolution for single molecules was successfully demonstrated using different imaging methods, including scanning tunneling microscopy, atomic force microscopy, cryogenic and transmission electron microscopy. In this perspective, we focus on different confinement strategies in these single-molecule imaging techniques, and summarize the recent studies of the structures and behaviors of single molecules. Especially, a new concept of spatial confinement at room temperature has been achieved by using microporous materials, such as zeolites, which has made it possible to fix and visualize the configurations of single molecule inside channels. In outlook, we describe what progress we can make along such a confinement strategy, and what new perspectives and discoveries we may find beyond our imagination.