The extent of the Earth’s surface burned annually by fires is affected by a number of drivers, including but not limited to climate. Other important drivers include the amount and type of vegetation (fuel) available and human impacts, including fire suppression, ignition, and conversion of burnable land to crops. Prior to the evolution of hominids, area burned was dictated by climate via direct influences on vegetation, aridity, and lightning. In the future, warming will be accompanied by changes in distribution, frequency, intensity, and timing of precipitation that may promote or suppress fire activity depending on location. Where area burned increases, fire may become self-regulating by reducing fuel availability. The effects of climate change on fire regimes will be strongly modulated by humans in many areas. Here, we use a systems approach to outline major drivers of changes in area burned. Due to the array of interacting drivers working in concert with climate’s influence on burned area, and uncertainty in the direction and magnitude of changes in these drivers, there is very high uncertainty for much of the globe regarding how fire activity and accompanying smoke emissions will change in the coming decades.