Abstract: Tumor cells use several metabolic pathways to support bioenergetic and biosynthetic demands of proliferation. In addition to glucose, glutamine is an important source of precursor substances and energy for cancer cell growth. Glutaminase (GSL) activity is associated with Ras, c-Myc, and other oncogenes, as well as Rho GTP enzyme. Many preclinical studies have confirmed that glutaminase inhibitors not only exhibit anti-tumor activity, but can also remarkably enhance the sensitivity of resistant cancer cells to targeted drugs. At present, the novel GSL inhibitor CB-839 has entered phase Ⅰ clinical trials and is expected to become a new drug for cancer treatment. This paper reviews the research progress on this novel glutaminase inhibitor and its antitumor activity.