Decades of research on the Aryl hydrocarbon Receptor (AhR) has unveiled its involvement in the toxicity of halogenated and polycyclic aromatic hydrocarbons, and a myriad of normal physiological processes. The molecular dissection of AhR biology has centered on a canonical signaling pathway in an effort to mechanistically reconcile the diverse pathophysiological effects of exposure to environmental pollutants. As a consequence, we now know that canonical signaling can explain many but not all of the AhR-mediated effects. Here we describe recent findings that point to non-canonical signaling pathways, and focus on a novel AhR interaction with the Krüppel-like Factor 6 protein responsible for previously un-recognized epigenetic changes in the chromatin affecting gene expression.