In addition to the six greenhouse gases included in the Kyoto Protocol, the tropospheric ozone precursors CO, NMVOC and NOx and the aerosols/aerosol precursors black carbon, organic carbon and SO2 also play significant roles in climate change. The aim of this paper is to review some of the main scientific and political challenges associated with incorporating tropospheric ozone and aerosol precursors into climate agreements, and to discuss how these challenges have a bearing on the design of future climate agreements. We argue that the optimal policy design for a particular substance depends on a combination of scientific and political concerns. We look particularly at regional climate effects, negative forcing, metrics (measuring climate effects against other gases on a common scale), political attractiveness, and verification and compliance. We systematically review the existing knowledge on these issues, explore their impact on policy design, and conclude that, with current scientific knowledge, CO and NMVOC could conceivably be included in a global climate agreement, either in a basket with the long-lived greenhouse gases or in a separate basket, while NOx and aerosols might be regulated more appropriately through regional agreements with links to a global agreement. However, the complexity and fairness implications of including tropospheric ozone precursors and aerosols might negatively affect the political feasibility of a future agreement.