Lyme disease (LD) is a tick-borne disease that typically presents with myalgia, fatigue, and a characteristic rash. LD occurs worldwide, and its incidence continues to increase. Prevention and early diagnosis based on increased understanding of disease transmission and pathomechanisms are crucial in stopping LD from progressing to its later stages. In this article, the first of a 2-part series on LD, we review epidemiologic and etiologic factors.