Background: Although asbestos in general is well known to cause a range of neoplastic and non-neoplastic human health effects, not all asbestos fiber types have the same disease causing potential and the modes of action (MOA) of specific types of asbestos and related fibers for various health outcomes are not well understood. Objectives: A workshop was held to discuss the state-of-the-science of the MOA for asbestos-related disease. The objective was to review the range of asbestos-induced health effects (including those at sites remote to the respiratory tract). We sought to identify existing knowledge gaps and define what research is needed to address these gaps and advance asbestos research. Discussion: Discussions centered on areas of uncertainty in the field, including how asbestos is defined and characterized, the role of different fiber characteristics (e.g., length and mineralogy) in disease and the impact of low-dose exposures on human health. Studying the dosimetry and mode of action of multiple fiber types would enhance our understanding asbestos-related disease. To better elucidate MOA of specific asbestos fibers, there is a need for data to inform the risk assessor as to asbestos' specific characteristics in determining fiber toxicity (e.g., surface area, mineral type, etc.), which may inform efforts to assess and control exposures and prevent adverse human health outcomes for the diverse range of fiber types. Specific research aims were defined for these topics and for overarching issues which should be addressed, including the use of standardized terminology, test materials and better experimental models to aid in data extrapolation to humans. To resolve these and other issues, there is a need for coordination between scientific disciplines to better understand the MOA leading to the various asbestos-related disease endpoints.