Evidence from environmental burden-of-disease studies can provide valuable input in the decision-making process in environmental health, facilitating priority setting and cost effectiveness evaluation. This paper discusses important aspects of environmental burden-of-disease estimates in the light of) published examples. To produce reliable and comparable burden-of-disease estimates for environmental and occupational risk factors, harmonized methods are needed. Such methods should address the feasibility of data collection at national, regional, and global levels, the reliability of estimates, the uncertainty around estimates, and scenario tools to investigate the health gains of options for preventive action in different domains of policy. Any such method will require a framework (i.e., causal inference model) able to take into account the contributions of distal and proximal causes, and the possible interactions between risk factors.