Grxs (glutaredoxins) are small ubiquitous redox enzymes. They are generally involved in the reduction of oxidative modifications using glutathione. Grxs are not only able to reduce protein disulfides and the low-molecular-mass antioxidant dehydroascorbate, but also represent the major enzyme class responsible for deglutathionylation reactions. Functional proteomics, including interaction studies, comparative activity measurements using heterologous proteins and structural analysis are combined to provide important insights into the crucial function of Grxs in cellular redox networks. Summarizing the current understanding of Grxs, with a special focus on organelle-localized members across species, genus and kingdom boundaries (including cyanobacteria, plants, bacteria, yeast and humans) lead to two different classifications, one according to sequence structure that gives insights into the diversification of Grxs, and another according to function within the cell that provides a basis for assessing the different roles of Grxs.