Vibrio parahaemolyticus, one of the Gram-negative common enteric pathogens, was first isolated in Japan in 1950. Since its discovery, this bacterium has been a major cause of food-poisoning in Japan, and its infection has recently undergone a global expansion. V. parahaemolyticus possesses a classical exotoxin, thermostable direct hemolysin, and two sets of type III secretion systems (T3SSs) that are able to inject effectors directly into host cells, which are its key virulence factors. Exotoxin/effector is exploited by many Gram-negative pathogens, and plays critical roles in pathogenesis by damaging host cells or by modulating host cell functions, through its activity on/in host cells. In recent years, functional activities of T3SS effectors produced by V. parahaemolyticus have been extensively studied, which has substantially increased our understanding of the pathogenic mechanisms of the bacterium. In paricular, some T3SS effectors of V. parahaemolyticus act as cytotoxins and thereby damage host cells. Here, I focus on these cytotoxic effectors of V. parahaemolyticus and describe recent advances in our understanding of their mechanisms of action.