Crude oil and its products, including light oils, heavy oils, fuels, tar, asphalt, lubricating oils, heavy oils, spilled oils, and hydrotreated oils, are complex mixtures containing thousands of chemical compounds with diverse structures. The chemical structural identification of crude oil and its products is extremely important for gaining insights into the chemistry of petroleum in the petrochemical industry. Mass spectrometry (MS), particularly ultrahigh-resolution MS (UHR-MS), is considered an important technique for the accurate analysis of the underlying mass and structure of crude oil components. Hydrogen/deuterium exchange (HDX) tandem MS and ionmobility (IM) spectrometry coupled with HR-MS have attracted significant attention for their application in investigating the molecular structures of petroleum and its products. The most effective HDX technique used for crude oil analysis is atmospheric pressure in-source HDX, which is suitable for the detailed structural identification of complex mixtures, such as crude oil. By combining atmospheric pressure ionization techniques, such as electrospray ionization (ESI), atmospheric-pressure photoionization (APPI), and atmospheric-pressure chemical ionization (APCI), the sample preparation step for HDX MS can be considerably simplified, enabling the attainment of highquality results and the specification of the heteroatom classes in crude oil. To isolate ions with specific m/z values and, thus, understand the core structures of oil compounds, the fragmentation patterns of the oil compounds are studied by tandem MS with collision-induced dissociation (CID) or infrared multiphoton dissociation coupled with HR-MS. In addition, IM separation with multiple cycles combined with quadrupole selection is considered a powerful technique for isolating ions with specific mobility values during complex mixture analysis. Recently, IM coupled with HR-MS, experimental collision cross-section (CCS) and theoretical CCS values was employed to study the chemical structures of petroleum compounds. Due to the separation of isomeric or isobaric ions in IM cells, improved peak capacities and highly accurate structural assignments of crude oil compounds can be achieved. This chapter provides an overview of some of the key applications of HDX, tandem MS, and IM-MS techniques to the structural analysis of crude oil and its products.