Shifts in future temperature and precipitation patterns will have profound effects on host-parasite interactions and the dynamics of disease in freshwater systems. The aims of this chapter are to present an overview of myxozoan disease dynamics in the context of climate change, and to illustrate how these might be predicted over the next several decades by developing a case study of disease dynamics of Ceratonova (syn Ceratomyxa) shasta in the Klamath River, California USA. Our case study introduces a model ensemble for predicting changes in disease dynamics under different climate scenarios (warm/dry, moderate/median, and cool/wet) from 2020 to 2060. The ensemble uses Global Circulation Models (GCMs) and basin scaled models for the Klamath River to generate predictions for future water temperature and river discharge. The environmental data are used as inputs for a predictive model and a degree day model to simulate effects of climate change on polychaete host populations and on C. shasta spore viability, respectively. Outputs from these models were then used to parameterize an epidemiological model to predict changes in disease dynamics under each climate scenario. The epidemiological model outputs were measured against baselines established using real data for low (2006), high (2008) and intermediate (2011) disease risk years. In general, the epidemiological model predicts that except for infrequent high discharge years, C. shasta dynamics will be