Display omitted •The xenobiotic response and hypoxia response pathways intersect.•Exposure to one stimulus can squelch the biological response to the other stimulus.•The signaling crosstalk between these pathways is frequently reciprocal.•Biological effectors of the responses, AhR and HIF1a, both use ARNT as a partner.•Normal xenobiotic responses may be perturbed under physiological hypoxia. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates many of the responses to toxic environmental chemicals such as TCDD or dioxin-like PCBs. To regulate gene expression, the AhR requires its binding partner, the aryl hydrocarbon receptor nuclear translocator (ARNT). ARNT is also required by the hypoxia-inducible factor-1α (HIF-1α), a crucial regulator of responses to conditions of reduced oxygen. The important role of ARNT in both the AhR and HIF-1α signaling pathways establishes a meaningful foundation for a possible crosstalk between these two vitally important signaling pathways. This crosstalk might lead to interference between the two signaling pathways and thus might play a role in the variety of cellular responses after exposure to AhR ligands and reduced oxygen availability. This review focuses on studies that have analyzed the effect of low oxygen environments and hypoxia-mimetic agents on AhR signaling and conversely, the effect of AhR ligands, with a special emphasis on PCBs, on HIF-1α signaling. We highlight studies that assess the role of ARNT, elucidate the mechanism of the crosstalk, and discuss the physiological implications for exposure to AhR-inducing compounds in the context of hypoxia.