BACKGROUND: Fires emit significant amounts of CO2 to the atmosphere. These emissions, however, are highly variable in both space and time. Additionally, CO2 emissions estimates from fires are very uncertain. The combination of high spatial and temporal variability and substantial uncertainty associated with fire CO2 emissions can be problematic to efforts to develop remote sensing, monitoring, and inverse modeling techniques to quantify carbon fluxes at the continental scale. Policy and carbon management decisions based on atmospheric sampling/modeling techniques must account for the impact of fire CO2 emissions; a task that may prove very difficult for the foreseeable future. This paper addresses the variability of CO2 emissions from fires across the US, how these emissions compare to anthropogenic emissions of CO2 and Net Primary Productivity, and the potential implications for monitoring programs and policy development. RESULTS: Average annual CO2 emissions from fires in the lower 48 (LOWER48) states from 2002-2006 are estimated to be 213 (+/- 50 std. dev.) Tg CO2 yr-1 and 80 (+/- 89 std. dev.) Tg CO2 yr-1 in Alaska. These estimates have significant interannual and spatial variability. Needleleaf forests in the Southeastern US and the Western US are the dominant source regions for US fire CO2 emissions. Very high emission years typically coincide with droughts, and climatic variability is a major driver of the high interannual and spatial variation in fire emissions. The amount of CO2 emitted from fires in the US is equivalent to 4-6% of anthropogenic emissions at the continental scale and, at the state-level, fire emissions of CO2 can, in some cases, exceed annual emissions of CO2 from fossil fuel usage. CONCLUSION: The CO2 released from fires, overall, is a small fraction of the estimated average annual Net Primary Productivity and, unlike fossil fuel CO2 emissions, the pulsed emissions of CO2 during fires are partially counterbalanced by uptake of CO2 by regrowing vegetation in the decades following fire. Changes in fire severity and frequency can, however, lead to net changes in atmospheric CO2 and the short-term impacts of fire emissions on monitoring, modeling, and carbon management policy are substantial.