This review will focus on how X-ray crystallographic studies of copper-containing amine oxidases have complemented the solution, kinetic, and spectroscopic research on this ubiquitous class of enzymes. These enzymes not only contain a copper ion at the active site, but also a unique organic cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ), which is absolutely required for catalysis. Structural data have not only shed light on the catalytic mechanism of the enzyme, which converts primary amines, using molecular oxygen, to aldehydes, ammonia, and hydrogen peroxide, but also on biogenesis of the cofactor. The cofactor is derived from a tyrosine in the enzyme amino acid sequence and requires only the addition of copper(II) and molecular oxygen in a self-processing event.