A common myth among the general public is that any substance derived from nature is inherently safe. To the contrary, some of the most potent and specifically‐targeted toxins have been identified and isolated from plants, mushrooms, and microorganisms. With regard to this volume, many of these toxins are of particular relevance in the pharmacokinetic study of xenobiotics, particularly their metabolism. This chapter highlights a select group of primarily small molecule toxins or protoxins of historical (i.e., aflatoxins) or contemporary (i.e., mycotoxins from “toxic mold”) relevance. Marine peptide toxins are intentionally omitted to maintain focus but are an additional class of highly‐selective acute and potentially lethal toxins from nature.