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Mononuclear, nonheme iron enzymes are known for their ability to mediate the oxidation of organic molecules in primary and secondary metabolism. One class of such enzymes is the diol dioxygenases that catalyze the oxidative cleavage of aromatic molecules. They come in two varieties, intradiol and extradiol, that add molecular oxygen symmetrically or asymmetrically, respectively. 3-Hydroxyanthranilate 3,4-dioxygenase (HAO) is a type III extradiol dioxygenase found in metabolic pathways related to breaking down tryptophan 2-nitrobenzoic acid. The product of HAO is unstable and either nonenzymatically cyclizes to quinolinic acid (QUIN), an endogenous neurotoxin and the universal precursor for NAD(P) biosynthesis, or is enzymatically processed, ultimately being fully oxidized to CO2 in the citric acid cycle. Elevation of QUIN is associated with neurodegenerative diseases, making HAO biomedically relevant. This article summarizes the history and current state of knowledge of the biochemistry of HAO. Recent studie that utilized X-ray crystallography of the in crystallo reactions coupled with various spectroscopies and activity measurements to elucidate much of the chemical mechanism catalyzed by HAO are highlighted.