Microsporidia are emerging fungi-like intracellular parasites of economic, veterinary and medical importance. The strategy they use to invade their host is related to the rapid extrusion of a unique and highly specialized organelle, the polar tube, which allows the injection of the infectious spore content within a target cell. This original process seems to be dependent on initial interactions between parasite and host cell components. The extreme reduction and compaction of most microsporidian genomes resulted in the loss of many metabolic pathways, which makes these parasites highly dependent on their host. Recent significant advances have been made in the understanding of mammal and insect immune responses against microsporidian infections with the involvement of both adaptive and innate immunity.