Human beings are constantly exposed to toxic chemicals present in food and the environment. We are also challenged by toxic byproducts of chemical reactions within our own bodies. These toxins need to be inactivated or excreted to maintain homeostasis. Pregnane X receptor (PXR) is a promiscuous nuclear receptor that is activated by a diverse array of endogenous and exogenous toxins. On activation, PXR regulates a number of target genes involved in drug metabolism and efflux in two key target tissues: the liver and intestine. In this article, we review the data accumulated in the last few years identifying PXR as a central player in the integration of these pathways.