Hypoxia-inducible factor-1 (HIF-1) is a critical regulator of the transcriptional response to low oxygen conditions (hypoxia/anoxia) experienced by mammalian cells in both physiological and pathophysiological circumstances. As our understanding of the biology and biochemistry of HIF-1 has grown, it has become apparent that cells adapt to signals generated by low oxygen through a network of stress responsive transcription factors or complexes, which are influenced by HIF-1 activity. This review summarizes our current understanding of the interaction of HIF-1 with AP-1, a classic example of a family of pleiotropic transcription factors that impact on diverse cellular processes and phenotypes, including the adaptation to low oxygen stress. The review focuses on experimental studies involving cultured cells exposed to hypoxia/anoxia, and describes both established and possible interactions between HIF-1 and AP-1 at different levels of cellular organization.