Among other constituents, manure contains pathogenic microorganisms that can cause serious illness and death in humans. The objective of this work is to review the status and challenges in modeling fate and water transport of manure-borne pathogens (MBP) and organisms-indicators of fecal contamination at pedon, hillslope, and watershed scales. Approaches used to model various aspects are critically evaluated, including (a) release of microorganisms from manure, (b) microorganism survival and inactivation in manure, soil, and surface water, (c) partitioning and attachment of pathogenic and indicator organisms to solid particles in runoff, soil, and sediment, and (d) transport with straining or entrapment in overland flow and in streams. The current challenges and research needs are outlined that include (a) the paucity of experimental data about the transport of pathogenic microorganisms, (b) the need to quantify potential and actual input of pathogens from wildlife, (c) uncertainty in background concentrations of indicator microorganisms, (d) better understanding of the effect of manure particulates on the MBP fate and transport, (e) relating the microorganism fate and transport parameters to environmental variables, such as soil and vegetation properties and weather parameters, (e) evaluating natural tracers with the transport behavior similar to microorganisms, e.g., manure-borne phosphorus, (f) understanding the uncertainty of the stream sampling data, (g) developing a process-based model of microorganism resuspension during the rainfall events, (i) developing upscaling techniques to utilize pedon and hillslope scale measurements and models in the watershed modeling, (j) a better insight into filtering function of vegetated buffer strips and riparian zones. Ensembles of simulations have to be made to estimate the possible distribution of simulation results and risks associated with a specific allocation of manure and manure management practices.