 The hypoxioinducible factor 1, HIF1, has been recognized as a crucial cancer drug target due to its strong correlation with tumor metastasis, angiogenesis, poor patient prognosis and resistance therapy. Hypoxic tumor cells activate several survival pathways, including the HIF1-alpha pathway, which is a crucial survival pathway for cancer cells. Recent advances in cancer biology have highlighted the development of novel strategies of cancer therapy targeting this important pathway, despite it being challenging to do so. This review summarizes the role and regulation of the HIF1-alpha in cancer and recent therapeutic approaches targeting this important pathway. This article was authored by Georgina N. Massoud and Whaley.