This chapter reviews the history of the human disease popularly known as plague, which has caused three major pandemics in the past two millennia, focusing on the most recent pandemic and the discovery of the insect that transmitted the disease. It begins with the Third Pandemic started in 1855, which began in Yunnan Province in southwestern China, an area rich in geological and biological diversity. Infections increased as the disease slowly spread to Hong Kong, where it reached epidemic levels in 1894. From there, maritime trade on steamships carried the plague to India, Australia, and then worldwide, to Africa, Europe, and the Americas. The chapter describes how, while the pandemic raged, scientists investigated the cause of the disease, learning that bacteria carried by Oriental rat fleas and rats were responsible. This pandemic killed at least 15 million people, mostly in India, and continued for nearly a century.