The history of multidecadal climate variability and drought in the United States during the past millennium is reviewed, and recent research into the physical mechanisms that produce long-term aridity is examined. Numerous multiyear droughts that have major social repercussions for contemporary and prehistoric societies can be identified in instrumental and proxy records. The 16th-century megadrought in the Southwest was the worst long period of aridity in the past 500 years. A prolonged period of aridity in the western United States from 900 to 1300 AD, which coincided with the Medieval Warm Period, is indicative of a mean shift in climate that ended in roughly 1400 AD. While the causes of these and other multiyear droughts are still under investigation, there is strong statistical and modeled evidence that persistent La Niña-like sea surface temperatures in the tropical Pacific force hemispheric and zonal symmetry in multidecadal droughts. In other words, persistent cooler than normal sea surface temperatures in the tropical Pacific force anomalous atmospheric circulations that produce multiyear droughts not only in the Great Plains and the Southwest, but also in the Mediterranean region of Europe, the Pampas region of South America, the steppes of Central Asia, and the outback of Western Australia. Other possible causes of long period drought include low-frequency variability in the north Pacific and Atlantic oceans and global warming in the Anthropocene.