Molluscan defense mechanisms are regulated to innate immunity, which is largely dependent on cellular components such as hemocytes possessing phagocytic and bactericidal activities. Among immune responses, apoptosis is an indispensable process because it enables the adequate clearance of damaged, senescent and infected cells without inflammation. Available information related to the molecular mechanisms of apoptosis has been accumulated for many molluscan species during the last decade. Almost all molluscan species live in an environment that changes incessantly according to microorganisms, industrial pollutants, temperature, and salinity. Such environmental factors might directly or indirectly induce apoptosis in molluscan cells. One type of apoptotic agent, reactive oxygen intermediates (ROIs), which are produced by a stress signal or phagocytosis, triggers apoptotic cell death in molluscan hemocytes. Dysfunction of ROI-mediated hemocytic apoptosis putatively causes disease morbidity and/or mortality when molluscan organisms are infected by pathogens. Furthermore, integrins have attracted attention for their unique functions because integrins regulate the phagocytic ability of molluscan hemocytes and induce hemocytic apoptosis. That process might be the result of ROI-generation. In this review, we summarize the roles and molecular mechanisms of apoptosis related to immunological functions of molluscan hemocytes.