The analysis of high-valent metal species has been in the focus of research for over 20 years. Mass spectrometry (MS) represents a technique routinely used for their characterization, in particular electrospray ionization mass spectrometry (ESI-MS) and cold-spray ionization-mass spectrometry (CSI-MS). The combination of both methods with tandem MS provides additional tools for understanding decay processes and reaction pathways. In this Perspective, tandem ESI-MS, an important instrument in enzyme and peptide characterization and organometallic chemistry, is discussed as a valuable tool for the elucidation of reaction mechanisms of high-valent metal species.