Microsporidia are pathogenic organism related to fungi. They cause infections in a wide variety of mammals as well as in avian, amphibian, and reptilian hosts. Many microsporidia species play an important role in the development of serious diseases that have significant implications in human and veterinary medicine. While microsporidia were originally considered to be opportunistic pathogens in humans, it is now understood that infections also occur in immune competent humans. Encephalitozoon cuniculi, Encephalitozoon intestinalis, and Enterocytozoon bieneusi are primarily mammalian pathogens. However, many other species of microsporidia that have some other primary host that is not a mammal have been reported to cause sporadic mammalian infections. Experimental models and observations in natural infections have demonstrated that microsporidia can cause a latent infection in mammalian hosts. This chapter reviews the published studies on mammalian microsporidiosis and the data on chronic infections due to these enigmatic pathogens.