Long time-horizon environmental risks with potential for global impacts have increased in visibility over the past several decades. Such issues as climate change, the nuclear fuel cycle, persistent synthetic chemicals, and stratospheric ozone depletion share some characteristics, including intergenerational impacts, strongly decoupled incidence of risks and benefits, substantial decision stakes and extreme uncertainty. What is not well understood are the similarities and differences among sources and implications of uncertainty among these global environmental threats, especially those associate with current and future human behavior. This describes the uncertainties associated with managing two global concerns: the nuclear (fission) fuel cycle and anthropogenic climate change. It finds that the two issue share some common uncertainties, some highly differentiated uncertainties and some interdependent uncertainty. It argues that these uncertainties preclude simple conclusions about the tradeoffs between risks from anthropogenic climate change and those from nuclear power. It concludes that a framework that treats uncertainty as an aspect of management, not as an analytical challenge, will both improve options for effective policy making and provide direction for useful (from a policy perspective) future research.