Safety implications of chemical reactions associated with postulated accident conditions with liquid metals (LM's) are discussed, along with possible prevention and mitigation techniques. The safety issues for handling lithium or 17Li83Pb are complex. However, enough is known to conclude that either LM can be safely used in deuterium—tritium fusion facilities if certain solutions can be implemented in designs at acceptable cost.The overall safety objective is to prevent significant accidental chemical reactions when possible and to mitigate the consequence of reactions that do occur. Passive design features should be used to limit maximum accident consequences, either facility damage from energy release or public health effects from radioactivity mobilization. Also, the total risk (consequence and frequency) of accidental chemical reactions should be limited.Available data on safety-related LM chemical reactions are reviewed, and the implications of reaction severity are indicated. Design suggestions and recommendations are offered to help meet safety objectives in LM fusion facilities. These suggestions are influenced by (a) the facility fluence, (b) the LM inventory, (c) the desired level of inherent/passive safety, and (d) the cost/benefit of design suggestions. Assuming a commercial-scale facility with large LM inventory with a goal of high levels of passive safety, recommendations for lithium designs include using nitrogen (rather than air) as the building atmosphere and a high reliability barrier covering concrete. Suggestions for either lithium or 17Li83Pb include eliminating water cooling within the building.