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Purpose Uncertainty is not always well captured, understood, or modeled properly, and can bias the robustness of complex relationships, such as the association between the environment and public health through exposure, estimates of geographic accessibility and cluster detection, to name a few. Methods We review current challenges and future opportunities as geospatial data and analyses are applied to the field of public health. We are particularly interested in the sources of uncertainty in geospatial data and how this uncertainty may propagate in spatial analysis. Results We present opportunities to reduce the magnitude and impact of uncertainty. Specifically, we focus on (1) the use of multiple reference data sources to reduce geocoding errors, (2) the validity of online geocoders and how confidentiality (e.g. HIPAA) may be breached, (3) use of multiple reference data sources to reduce geocoding errors, (4) the impact of geoimputation techniques on travel estimates, (5) residential mobility and how it affects accessibility metrics and clustering, and (6) modeling errors in the American Community Survey. Our paper discusses how to communicate spatial and spatiotemporal uncertainty, and high performance computing to conduct large amounts of simulations to ultimately increase statistical robustness for studies in public health. Conclusions Our paper contributes to recent efforts to fill in knowledge gaps at the intersection of spatial uncertainty and public health.