Elucidating connectivity and functionality at the whole-brain level is one of the most challenging research goals in neuroscience. Various whole-brain optical imaging technologies with submicron lateral resolution have been developed to reveal the fine structures of brain-wide neural and vascular networks at the mesoscopic level. Among them, micro-optical sectioning tomography (MOST) is attracting increasing attention, as a variety of technological variations and solutions tailored toward different biological applications have been optimized. Here, we summarize the recent development of MOST technology in whole-brain imaging and anticipate future improvements.