A consideration of available evidence for some known and well-characterized waterborne pathogens suggests that the diversity of pathogen virulence mechanisms and properties is too great to specifically predict the emergence and future human health impacts of new waterborne pathogens. However, some future emerging pathogens are existing microbes that will be discovered to cause disease. Some will arise from existing ones by either predictable evolutionary and adaptation changes or by unpredictable changes involving a variety of biotic and abiotic mechanisms. Many, and perhaps most, emerging waterborne human pathogens will be zoonotic agents or come from other non-human reservoirs. The emergence of some waterborne pathogens will be related to antibiotic use, resulting in emerging antibiotic-resistant waterborne pathogens. Reliably predicting pathogen emergence and human health effects based on VFARs or other properties of microbes and their hosts is not possible at this time. This is because of (1) the diversity of microbes and their virulence and pathogenicity properties, (2) their ability to change unpredictably, (3) their intimate and diverse interrelationships with a myriad of hosts and dynamic natural and anthropogenic environments and (4) the subtle variations in the immune status of individuals. The best available approach to predicting waterborne pathogen emergence is through vigilant use of microbial, infectious disease and epidemiological surveillance. Understanding the microbial metagenome of the human body can also lead to a better understanding of how we define and characterize pathogens, commensals and opportunists.