Lipoxygenases (LOX) are found in a wide variety of organisms, from plants to humans. LOX is an iron-based dioxygenase which activates the substrate instead of molecular oxygen to form the hydroperoxide product. This reaction is achieved by the abstraction of a hydrogen atom from the relatively low energy methylene carbon in a 1,4-diene subunit. The subsequent radical is attacked by molecular oxygen with hydrogen atom addition as the final step. The ability of the active site iron to abstract the hydrogen atom is highly dependent on both the primary and secondary coordination environment, as demonstrated by mutagenesis. While the reactivity of the active site iron is of relatively low impact, the relative selectivity of the active site cavity is of high impact. Humans have three major LOX isozymes, defined by the oxidized carbon on arachidonic acid (AA). The LOX-products of AA are involved in many human diseases, such as cancer, diabetes, heart attacks and stroke, to name a few. The focus of the Holman lab is to not only develop LOX inhibitors to study LOXs role in human disease but also investigate the biological relevancy of non-canonical fatty acids, such as DHA, EPA, LA and DGLA. Utilizing this two-pronged approach, we will discuss our discovered inhibitors as well as our nanomolar LOX products with respect to their role in human disease.