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Hypoxia, a common consequence of solid tumor growth in breast cancer and other cancers, serves to propagate a cascade of molecular pathways which include angiogenesis, glycolysis, and alterations in microenvironmental pH. Hypoxia‐inducible factors, heterodimeric DNA binding complexes composed of two subunits, provide critical regulation of this response. This review presents a synopsis of the genes induced by hypoxia in the context of breast cancer and discusses how upregulation of HIF‐1 activity, and the homologous factor HIF‐2, are not only fundamental for the adaptation to hypoxia but also may be critical for tumor progression. Microsc. Res. Tech. 59:41–48, 2002. © 2002 Wiley‐Liss, Inc.