This chapter relates how yellow fever continued to cause casualties during the US occupation after the Spanish-American War ended and how Major William Crawford Gorgas created a successful strategy to eliminate the disease from Cuba by attacking mosquito breeding sites. It goes on to tell the story of the plan to link the Atlantic and Pacific Oceans, proposed earlier that century, with the Panama Railroad transporting military goods and soldiers, plus those seeking gold in California. A canal was proposed, but the first, French effort to build it cost hundreds of millions of dollars and tens of thousands of workers’ lives lost before capitulating to yellow fever in 1889. Subsequent US construction, begun in 1904, was soon threatened by disease. When Colonel Gorgas brought his yellow fever control plan to Panama he faced criticism from his superiors but gained the support of President Theodore Roosevelt. The chapter relates how his plan, though seemingly improbable, worked, defeating yellow fever, saving countless lives, and allowing the completion of the canal.