This review focuses on the effect of mangiferin on: (1) inflammation, with respect to NFκB, PPARү and the immune system; (2) cell cycle, the MAPK pathway G2/M checkpoint; (3) proliferation and metastasis, and implications on β-catenin, MMPs, EMT, angiogenesis and tumour volume; (4) apoptosis, with a focus on Bax/Bcl ratios, intrinsic/extrinsic apoptotic pathways and telomerase activity; (5) oxidative stress, through Nrf2/ARE signalling, ROS elimination and catalase activity; and (6) efficacy of chemotherapeutic agents, such as oxaliplatin, etoposide and doxorubicin. The gene discussed is NFKB1; the disease is neoplasm.