The muskrat (Ondatra zibethicus) is a prominent and wide-spread furbearer in North America. Historically valued for their waterproof pelts and abundance of capture, muskrats have been trapped for their fur in North America for centuries. However, evidence of a decline of muskrat harvest since 1970 has been observed across the United States. Theories as to why populations declined include habitat loss, increased flooding events, predation, environmental contamination, and disease. Two of these theories, environmental contamination and disease, can directly affect the physical health of individual muskrat. Disease transmission between individual muskrats and muskrat populations may be influenced by various components of muskrat ecology (e.g. semi-colonial behavior). Therefore, it is important to not only understand the prevalence of specific pathogens, diseases, and contaminants that muskrats are exposed to, but also to understand the role that muskrat ecology plays in population health. To address these knowledge gaps, I employed a multifaceted approach to define pathogens, diseases and contaminants of muskrats, including: 1) retrospective study of published data on muskrat diseases in North America; 2) review of diagnostic data on muskrats in the Eastern United States in combinations with active surveys of diseases and pathogens of trapper-killed muskrats throughout Pennsylvania, and 3) a telemetry study in Pennsylvania to characterize survival and ecological factors of muskrats that may influence disease transmission. In Chapter 1, I conducted a literature review on muskrat parasites, pathogens, and disease across their natural range. This review was comprised of 129 articles from 1915 to 2019. Reports included were from 27 U.S. states and 9 Canadian provinces, and cover the following disease etiologies: parasites, bacteria, viruses, and contaminants. Several notable diseases and pathogens causing mortality in muskrats were cysticercosis, tularemia (Francisella tularensis), and Tyzzers disease (Clostridium piliforme). I identified gaps in the literature, specifically relating to biotoxin poisoning and impacts of both agricultural and chemical contamination on muskrat health. The retrospective study provided a basis for further investigations in this study. In Chapter 2, I built upon previous literature based on passive surveillance which was comprised of reviewing diagnostic cases of muskrats from the Southeastern Cooperative Wildlife Disease Study. Aside from trauma, the main causes of mortality in the diagnostic cases were Tyzzers disease and cysticercosis. These commonalities, along with existing knowledge gaps identified during the retrospective study, provided me with the foundation for components to examine using active surveillance. I collected 380 muskrat carcasses from across Pennsylvania to examine exposure to bacterial (C. piliforme, F. tularensis) and parasite (Toxoplasma gondii, Babesia spp., intestinal parasites) infections as well as heavy metal contamination. I detected Tyzzers disease, sarcosystosis, and toxoplasmosis at low prevalence. I failed to detect tularemia, babesiosis, or cadmium, arsenic, and mercury contamination. Parasite burdens were typical of historic reports, however younger muskrats had larger burdens than older muskrats which is contradictory to what was observed in Pennsylvania in 1966. The Northcentral and Northwest regions had higher parasite burdens than all of the southern regions combined (P