Paralytic shellfish toxins (PSTs) are natural toxins produced by some microorganisms, especially during harmful algal blooms (HABs). Molluscs and other marine animals can accumulate significant amounts of these toxins, causing food poisoning. Due to the seriousness of this poisoning, the European Union has established a concentration limit and an official method based on liquid chromatography for their analysis. PSTs are very challenging analytes due to their very high polarity and occurrence of different isomers with varying toxicity towards humans. Current available extraction methods are adapted from a previous existing bioassay and not fully validated yet. Recovery efficiencies of the extraction procedure are occasionally low, and further clean-up can lead to highly variable results depending on the toxin and the matrix analysed. Detection of PSTs by mass spectrometry offers the ability to identify all toxins in a single analysis, which is an improvement over the current official method based on fluorescence detection prior derivatisation. As a drawback, normal phase chromatography is required, which tend to be less robust that more conventionally used reversed-phase chromatography used in the official method. New extraction techniques and recent advances in the mass spectrometry field (e.g., high-resolution mass spectrometry and ion mobility) have been barely applied yet to the analysis of PSTs. An increase in the frequency and extension of HABs due to global warming will lead to more severe impacts on health, environment and economy in coastal areas. An improvement of current existing analytical methods is therefore needed to allow for a faster and more accurate monitoring of PSTs.