One of the most promising approaches to addressing the challenges of securing cheap and renewable energy sources is to design catalysts from earth abundant materials capable of promoting key chemical reactions including splitting water into hydrogen and oxygen (2H(2)O -> 2H(2) + O-2) as well as both the oxidation (H-2 -> 2H(1)) and reduction (2H(1) -> H-2) of hydrogen. Key to elucidating the origin of catalytic activity and improving catalyst design is determining molecular-level structure, in both the 'resting state' and in the functioning 'active state' of the catalysts. Herein, we explore some of the analytical challenges important for designing and studying new catalytic materials for making and using hydrogen. We discuss a case study that used the combined approach of X-ray absorption spectroscopy and transmission electron microscopy to understand the fate of the molecular cluster, [Mn4O4L6](+), in Nafion.