Optical　molecular　imaging　has　been　rapidly　developed　to　noninvasively　visualize　in　vivo　physiological　and　pathological　processes　involved　in　normal　and　suffering　organisms　at　the　cellular　and　molecular　levels,　in　which　advanced　optical　imaging　technology　and　modern　molecular　biology　are　being　combined　to　provide　a　state-of-the-art　tool　for　preclinical　biomedical　research.　Among　optical　molecular　imaging　modalities,　bioluminescence　tomography　(BLT)　has　experienced　considerable　growth　and　attracted　much　attention　in　recent　years　for　its　excellent　performance,　unique　advantages,　and　high　cost-effectiveness.　This　article　focuses　on　the　genesis　and　development　of　BLT,　especially　for　its　computational　methodology,　imaging　system,　and　biomedical　application.　An　overview　of　the　advantages　and　challenges　of　the　conventional　planar　bioluminescence　imaging　technique　is　first　described　in　comparison　with　currently　available　molecular　imaging　modalities.　The　imaging　algorithms　for　inverse　source　reconstruction　are　classified　and　summarized　according　to　different　a　priori　knowledge,　followed　by　a　simple　depiction　of　the　uniqueness　theorems　of　BLT　solution.　Diverse　imaging　systems　for　obtaining　three-dimensional　quantitative　information　of　internal　bioluminescent　sources　are　then　reviewed.　The　latest　application　examples　of　BLT　in　tumor　study　and　drug　discovery　are　introduced　and　compared　with　other　mature　imaging　technologies.　Finally,　the　paper　is　concluded　and　an　attractive　prospect　for　BLT　ispredicted.