Mathematical and statistical models are needed to understand the extent to which weather, climate variability, and climate change are affecting current and may affect future health burdens in the context of other risk factors and a range of possible development pathways, and the temporal and spatial patterns of any changes. Such understanding is needed to guide the design and the implementation of adaptation and mitigation measures. Because each model projection captures only a narrow range of possible futures, and because models serve different purposes, multiple models are needed for each health outcome (‘horses for courses’). Multiple modeling results can be used to bracket the ranges of when, where, and with what intensity negative health consequences could arise. This commentary explores some climate change and health modeling issues, particularly modeling exposure-response relationships, developing early warning systems, projecting health risks over coming decades, and modeling to inform decision-making. Research needs are also suggested.