The azaspiracids (AZAs) are a group of marine phycotoxins discovered during the second half of the 1990s. Several cases of human intoxication due to the presence of AZAs in shellfish have been reported, with gastrointestinal symptoms. Toxicological studies in vivo and in vitro have revealed that various cell types are sensitive to AZA toxicity; however, the biological target of the toxin is still unknown. One of the in vitro signs of AZA toxicity is the alteration of the actin cytoskeleton arrangement, which is accompanied by changes in cell shape and loss of cell adherence to the substrate. Moreover, the cytoskeletal damage is irreversible after toxin withdrawal. Several other in vitro effects of AZAs have been described that could be related to cytoskeletal changes, such as E-cadherin degradation, caspase activation/apoptosis, membrane cholesterol reduction, or gene expression alterations, although evidence for a direct relationship between any of these effects and AZA-induced cytoskeletal damage is still nonexistent.