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Reorganization of cellular metabolism is one of the hallmarks of cancer and many tumors show high glucose uptake and glutamine addiction. Glutamine is imported by the SLC family transporters from the microenvironment, and ASCT2 (encoded by the SLC1A5 gene) is recognized as a primary transporter. Of note, ASCT2 is overexpressed in different cancers and is closely related to poor prognosis. Nonetheless, the mechanisms regulating ASCT2 activity has not been elucidated. Moreover, several inhibitors of ASCT2 have emerged and shown a surprising antitumor effect. In conclusion, this review describes the function, regulatory mechanism, and inhibitors of ASCT2 in cancer, suggesting that high expression of ASCT2 is a promising prognostic marker and a potential drug target.