The perceived threat of the use of nerve agents by terrorists against civilian targets implies the need for methods for point-of-care (POC) diagnosis. This review presents an overview of methods that are currently available for the assessment of exposure to nerve agents. Since these methods are mostly MS based, they require complex and expensive equipment and well-trained personnel and, consequently, they are not very suitable for rapid POC diagnosis. However, new technologies are emerging that allow, among others, immunochemical detection of acetylcholinesterase inhibited by nerve agents. Also, lab-on-a-chip methodologies are under development. It is anticipated that MS methods will be suitable for POC diagnosis within a few years, due to the miniaturization of equipment and the emergence of methodologies that enable mass spectrometric analysis with little sample pretreatment and that are potentially fieldable, such as direct analysis in real time and desorption electrospray ionization MS.