Hydroclimatological and anthropogenic factors are key drivers of waterborne disease transmission. Information on human settlements and host mobility on waterways along which pathogens and hosts disperse, and relevant hydroclimatological processes, can be acquired remotely and included in spatially explicit mathematical models of disease transmission. In the case of epidemic cholera, such models allowed the description of complex disease patterns and provided insight into the course of ongoing epidemics. The inclusion of spatial information in models of disease transmission can aid in emergency management and the assessment of alternative interventions. Here, we review the study of drivers of transmission via spatially explicit approaches and argue that, because many parasitic waterborne diseases share the same drivers as cholera, similar principles may apply.