This issue ofPhilosophical Transactionsexamines the relationship between scientific uncertainty about climate change and knowledge. Uncertainty is an inherent feature of the climate system. Considerable effort has therefore been devoted to understanding how to effectively respond to a changing, yet uncertain climate. Politicians and the public often appeal to uncertainty as an argument to delay mitigative action. We argue that the appropriate response to uncertainty is exactly the opposite: uncertainty provides an impetus to be concerned about climate change, because greater uncertainty increases the risks associated with climate change. We therefore suggest that uncertainty can be a source of actionable knowledge. We survey the papers in this issue, which address the relationship between uncertainty and knowledge from physical, economic and social perspectives. We also summarize the pervasive psychological effects of uncertainty, some of which may militate against a meaningful response to climate change, and we provide pointers to how those difficulties may be ameliorated.