Methane (CH4) is the most important greenhouse gas after water vapor and carbon dioxide (CO2), and wetlands represent its largest natural source. But the high spatial and temporal variability of CH4 emissions from natural wetlands combined with patchy and incomplete information on global wetland distribution makes them especially difficult to quantify. CH4 from natural wetlands still has the largest uncertainty of any CH4 source. This is of concern because projections for the future suggest a rise in CH4 emissions and thus a positive feedback in climate change. We also know from ice cores that atmospheric CH4 concentration has varied by a factor of 2, at orbital and suborbital frequencies, during the past 400,000 years. The causes of these variations are largely unknown, but it is likely that variations in wetland extent and productivity due to changes in glaciation, sea level, atmospheric CO2 concentration, and climate played a part. Other mechanisms, including changes in the oxidation capacity of the atmosphere and pulsed releases from marine and terrestrial gas hydrates, may have contributed as well. None of these mechanisms is adequately quantified.