Enterotoxigenic E. coli (ETEC) and Shigella are enteropathogens causing significant global morbidity and mortality, particularly in low-income countries. No licensed vaccine exists for either pathogen, but candidates are in development, with the most advanced candidates potentially approaching pivotal efficacy testing within the next few years. A positive policy recommendation for introduction of any vaccine, following licensure, depends on evidence of vaccine cost-effectiveness and impact on morbidity and mortality. The mortality estimates for these two pathogens have fluctuated over recent years, which has led to uncertainty in the assessment of their relative public health importance for use in low and middle-income countries. This paper summarizes the various ETEC and Shigella disease burden estimates, based on a review of current literature and informal consultations with leading stakeholders in enteric disease modelling. We discuss the factors that underpin the variability, including differences in the modelling methodology; diagnostic tools used to ascertain diarrheal etiology; epidemiological setting; the data that are available to incorporate; and absolute changes in the total number of diarrheal deaths over time. We consider the further work that will strengthen the evidence needed to support future decision making with respect to recommendations on the relative utility of these vaccines.