Globally, almost three billion people rely on biomass (wood, charcoal, crop residues, and dung) and coal as their primary source of domestic energy. Exposure to indoor air pollution from the combustion of solid fuels has been implicated, with varying degrees of evidence, as a causal agent of of disease and mortality in developing countries. We review the current knowledge on the relationship between indoor air pollution and disease, and on the assessment of interventions for reducing exposure and disease. Our review takes an environmental health perspective and considers the details of both exposure and health effects that are needed for successful intervention strategies. We also identify knowledge gaps and detailed research questions that are essential for successful design and dissemination of preventive measures and policies. In addition to specific research recommendations, we conclude that given the central role of housing, household energy, and day-to-day household activities in determining exposure to indoor smoke, research and development of effective interventions can benefit tremendously from integration of methods and analysis tools from a range of disciplines—from quantitative environmental science and engineering, to toxicology and epidemiology, to the social sciences.