The catalysis science of mixed metal oxides (supported metal oxides, molecular sieves and bulk mixed metal oxides) has undergone dramatic paradigm changes over the past 25 years as new characterization techniques became available (X-ray absorption spectroscopy (EXAFS/XANES/soft XANES), Raman, solid-state NMR, HR-TEM, UV–vis DRS and LEISS) to catalysis researchers. The major advantages offered by these spectroscopic improvements are that (1) they can detect XRD inactive amorphous surface metal oxide phases as well as crystalline nanophases and (2) their ability to collect information under various environmental conditions. Application of these spectroscopic techniques to the investigation of mixed metal oxide catalysts have provided new fundamental insights into the electronic and molecular structures of mixed metal oxide catalytic active sites and how they control the catalytic activity and selectivity characteristics. The most significant discovery has been that amorphous metal oxide phases are always present and are the catalytic active sites for many applications of mixed metal oxide catalysts. This has resulted in a significant paradigm shift as to how mixed metal oxide catalytic materials function for different applications. This article reviews the instrumental advances and the resulting conceptual advances that have evolved over the past 25 years in the catalysis science of mixed metal oxide catalysts.