Using X-ray crystallography, we are determining the high-resolution structures of enzymes that contribute to the oxidative folding of substrate proteins. Through these structures, we are gaining insights into the mechanisms by which disulfide formation is executed and regulated in compartments of the secretory pathway. Capturing disulfide catalysts in different crystal forms and studying various mutant enzymes have suggested points where conformational changes play important roles in enzyme activity. For example, capturing the Ero1 enzyme from the yeast endoplasmic reticulum in multiple states showed how the redox-active disulfide that directly oxidizes protein disulfide isomerase is present on a flexible loop that flips in and out of the catalytic core of the enzyme. A similar theme, with the conformational changes occurring on the scale of entire domains, occurs in the QSOX enzyme family.