The chemical characteristics of formaldehyde make it widely used and important in the global economy. It has applications in the health area and in various industrial sectors. However, formaldehyde is considered toxic substance and is classifed as a persistent organic pollutant. Direct and prolonged contact with formaldehyde can cause serious damage to the body and may even lead to death. It is classifed by several agencies as a human carcinogen and may exhibit mutagenic/teratogenic efects and/or damage the endocrine system. Various matrices have been found to contain formaldehyde at concentrations higher than those permited by global health regulatory agencies. To this end, mass spectrometry can provide a very useful tool, enabling the identifcation and quantifcation of formaldehyde. Although various analytical techniques can be used for the determination and quantifcation of volatile organic compounds, chromatography is one of the most widely used methods due to its precision. Coupled to a detection system such as mass spectrometry, it can be employed for the determination of compounds potentially toxic to humans, including formaldehyde. The purpose of this chapter is to summarize some recent and important studies concerning the quantifcation of formaldehyde using mass spectrometry as a powerful analytical tool.