Due to its unique properties, amorphous silicon dioxide (a-SiO2) or silica is a key material in many technological fields, such as high-power laser systems, telecommunications, and fiber optics. In recent years, major efforts have been made in the development of highly transparent glasses, able to resist ionizing and non-ionizing radiation. However the widespread application of many silica-based technologies, particularly silica optical fibers, is still limited by the radiation-induced formation of point defects, which decrease their durability and transmission efficiency. Although this aspect has been widely investigated, the optical properties of certain defects and the correlation between their formation dynamics and the structure of the pristine glass remains an open issue. For this reason, it is of paramount importance to gain a deeper understanding of the structure–reactivity relationship in a-SiO2 for the prediction of the optical properties of a glass based on its manufacturing parameters, and the realization of more efficient devices. To this end, we here report on the state of the most important intrinsic point defects in pure silica, with a particular emphasis on their main spectroscopic features, their atomic structure, and the effects of their presence on the transmission properties of optical fibers.