Organic toxic substances, consisting of natural and synthetic toxins, are diverse in structure and toxicity. In poisoning cases, such toxins can be determined using a variety of analytical methods. Mass spectrometry is superior for obtaining structural information. Low molecular weight (MW) lipophilic toxins can be analyzed by gas chromatography-mass spectrometry (GC-MS), as exemplified by chemical warfare agents. Low MW polar toxins and metabolites of lipophilic toxins can be also determined by GC-MS after conversion to volatile derivatives. Liquid chromatography (LC)-MS with electrospray ionization (ESI) or atmospheric pressure chemical ionization can be used in the direct analysis for polar low MW toxins, even though the chromatographic peak resolution is low, as exemplified by saxitoxin. Intermediate MW (around 1000) polar toxins can be analyzed by matrix-assisted laser desorption ionization (MALDI)-time-of-flight (TOF)-MS and LC-ESI/MS, and the associated MS/MS technique, which permits structural information, such as the peptide sequence to be obtained. High MW proteinous toxins can be also analyzed by LC-MS and MALDI-TOF-MS, as exemplified by staphylococcal enterotoxin B. However, only an approximate MW estimation can be obtained for ricin, because of the difficulty of obtaining accurate MW values, due to the presence of multiple monoisotopic molecular ion peaks and heterogeneity as the result of posttranslational modification. Instead, LC-MS/MS analysis after proteolytic digestion is typically used in the identification of digested intermediate MW peptides and the subsequent sequencing of the ricin protein.