X-ray luminescence computed tomography(XLCT) is an emerging hybrid imaging modality that can be used as a new tool in molecular imaging. XLCT has the potential to achieve the high spatial resolution of X-ray imaging and the high sensitivity feature of optical imaging in deep tissues. In XLCT,high energy X-ray photons are used to excite X-ray excitable particles emitting optical photons to be measured for reconstruction of the particle distribution inside tissues. Numerical simulations and experimental studies have been performed and proved that XLCT is suitable for in vivo small animal imaging. The aim of this review paper is to introduce the background of XLCT and to detail the concept of XLCT,including a brief review of tw o types of XLCT imaging system designs. The major challenges in the development of XLCT are also described. Finally,the future applications and development directions of XLCT are discussed. X-ray luminescence computed tomography (XLCT) is an emerging hybrid imaging modality that can be used as a new tool in molecular imaging. XLCT has the potential to achieve the high spatial resolution of X-ray imaging and the high sensitivity feature of optical imaging in deep tissues. In XLCT, high energy X-ray photons are used to excite X-ray excitable particles emitting optical photons to be measured for reconstruction of the particle distribution in tissues. Numerical simulations and experimental studies have been performed and proved that XLCT is suitable for in vivo small animal imaging. The aim of this review paper is to introduce the background of XLCT and to detail the concept of XLCT, including a brief review of tw o types of XLCT imaging system designs. The major challenges in the development of XLCT are also described. Finally, the future applications and development directions of XLCT are discussed.