The effects of global climate change on human health are being widely studied with the goal of preventing outbreaks of new or re-emerging infectious diseases. The focus of this study is plague, which is classified by the World Health Organization as a re-emerging disease. Correlations between past climate and corresponding plague cases were analyzed to determine possible links that could be used to forecast future plague prevalence. Regional climate indices were compared to the number of human plague cases in Africa, Asia, and the Americas, and annual county climate data was compared to the plague cases in New Mexico and Arizona. The most significant correlations were found between the Pacific Decadal Oscillation and plague cases in Africa and the United States, specifically Arizona, California and New Mexico. Most likely there is a combination of climatic, biologic, chemical and anthropogenic factors that determines the prevalence and distribution of plague.