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Perkinsus marinus is a facultative intracellular marine protozoan parasite responsible for the Dermo disease in Crassostrea virginica oysters. Associated with mass mortalities in the Gulf Coast and Chesapeake Bay (USA), it remains one of the main hurdles for oyster reef restoration and aquaculture. Oysters take up the parasite by filter-feeding; in the pallial cavity, it can be phagocytosed by the hemocytes via CvGal1, gaining access to the internal milieu. Inside the parasitophorous vacuole, the parasite resists oxidative stress and acquires nutrients. Propagation strategies include binary fission, budding, palintomy, and schizogony. Although the effect on humans upon consumption of raw infected oysters has not been studied, humanized HLA-DR4 mice fed with P. marinus do not develop noticeable pathology but elicit systemic immunity. Parasite culture in host-free media, and the use of genetic tools, make it a tractable genetic model and a heterologous expression and vaccine-delivery system.