Microsporidians are unicellular eukaryotic obligate intracellular parasites that cause infections in a wide range of metazoan hosts from terrestrial and aquatic environments. A few genera of microsporidia have been reported to infect shellfish, including shrimp. Further, several aquatic microsporidians have been associated with severe economic impacts in the aquaculture industry, most commonly the members of the Enterocytozoon Group Microsporidia. The disease caused by the microsporidian parasite Enterocytozoon hepatopenaei (EHP), termed hepatopancreatic microsporidiosis (HPM), has become a major problem in the shrimp farming sector in many Southeast Asian countries. Recently, the shrimp microsporidian Enterocytozoon hepatopenaei has been redescribed as Ecytonuceospora hepatopenaei (EHP) based on morphological and molecular analysis. However, to avoid confusion, the microsporidian is referred to in this chapter as Enterocytozoon hepatopenaei. EHP mainly targets the hepatopancreas resulting in growth retardation and increased size variation in whiteleg shrimp P. vannamei. Many aquatic macrofauna, including artemia, molluscs, mussels, polychaetes, crabs, and freshwater prawns, have tested positive for EHP and act as carriers of the disease. The major route of transmission is reported to be horizontal through cannibalism and cohabitation. Several diagnostic approaches, including advanced molecular methods, have evolved for the rapid detection and quantification of the parasite. Several researchers have elucidated the host–pathogen interaction through metabolomic, proteomic, metagenomic, and transcriptomic studies. The adoption of better management practices, biosecurity at farms and hatcheries, and standardized therapeutics have been proposed as effective preventive measures for managing EHP.