Among other things, the wide-scale development and use of nanomaterials is expected to produce costly regulatory and civil liabilities for nanomanufacturers due to lingering uncertainties, unanticipated effects, and potential toxicity. The life-cycle environmental, health, and safety (EHS) risks of nanomaterials are currently being studied, but the corresponding legal risks have not been systematically addressed. With the aid of a systematic approach that holistically evaluates and accounts for uncertainties about the inherent properties of nanomaterials, it is possible to provide an order of magnitude estimate of liability risks from regulatory and litigious sources based on current knowledge. In this work, we present a conceptual framework for integrating estimated legal liabilities with EHS risks across nanomaterial life-cycle stages using empirical knowledge in the field, scientific and legal judgment, probabilistic risk assessment, and multicriteria decision analysis. Such estimates will provide investors and operators with a basis to compare different technologies and practices and will also inform regulatory and legislative bodies in determining standards that balance risks with technical advancement. We illustrate the framework through the hypothetical case of a manufacturer of nanoscale titanium dioxide and use the resulting expected legal costs to evaluate alternative risk-management actions.