Isoliquiritigenin is a chalcone with a wide variety of targets; it exhibits anticancer, anti-angiogenic, antioxidative, and neuroprotective activities. Isoliquiritigenin inhibits NMDA receptors, histone deacetylases (HDACs), VEGFR2, and NF-κB (via inhibition of IκB kinase). In vitro, this compound increases Nrf2 expression. Additionally, isoliquiritigenin downregulates expression of arachidonic acid-metabolizing enzymes cyclooxygenase-2 (COX-2) and phospholipase A2 (PLA2), increasing mitochondria- and/or caspase-mediated apoptosis, and inhibiting proliferation of breast cancer cells. Isoliquiritigenin also modulates sirtuins and acts as a positive allosteric modulator at GABA-A receptors.