This chapter discusses methods that are intended to be used for research purposes such as the detection and structure elucidation of new toxins or toxin metabolites. Marine biotoxins can be divided into two different classes: hydrophilic and lipophilic marine biotoxins. The chapter discusses the various liquid chromatography (LC)-mass spectrometry methods for hydrophilic marine biotoxins and the traditional lipophilic marine biotoxins, such as diarrheic Shellfish poisoning toxins, azaspiracid Shellfish poisoning toxins, pectenotoxins, and yessotoxins. All these toxins show a similar retentive behavior in LC systems, and therefore these toxins are often analyzed in a single multitoxin analysis. Mass spectrometric analysis methods for paralytic shellsh poisoning toxins and the application in Shellfish monitoring programs are still in their infancy. For the diarrheic Shellfish poisoning toxins, several studies have been conducted on the fragmentation of okadaic acid by using various types of ionization such as fast atom bombardment, thermospray, ion spray, and electrospray, where the latter is nowadays used most frequently.