CD317 (also known as tetherin, BST-2, or HM1.24) was first discovered from a human plasma cell line in 1994 and defined as a novel terminal B-cell-restricted antigen. It was first reported to be a potent interferon-induced host antiviral factor in 2008, and was demonstrated that it inhibited the release of HIV-1 viral particles deficient in the viral membrane protein Vpu. Since that time, numerous reports have been published regarding to the structure, the antiviral activity and immunological properties of this protein. Moreover, some new functions of CD317, such as involvement with tumor development and exosome tetherin, have been found recently. Thus, CD317 function is not just limited to the antiviral field. In this review, the antiviral function, oncobiology and signal transduction of CD317 were summarized, which will enhance the overall knowledge of CD317 function during viral infection and cancer metastasis, possibly leading to unique therapeutic applications for these diseases.