%0 Journal Article %T Hitchhiker's Guide to Borrelia burgdorferi. %A Bourgeois JS %A Hu LT %J J Bacteriol %V 0 %N 0 %D 2024 Aug 14 %M 39140751 %F 3.476 %R 10.1128/jb.00116-24 %X Don't Panic. In the nearly 50 years since the discovery of Lyme disease, Borrelia burgdorferi has emerged as an unlikely workhorse of microbiology. Interest in studying host-pathogen interactions fueled significant progress in making the fastidious microbe approachable in laboratory settings, including the development of culture methods, animal models, and genetic tools. By developing these systems, insight has been gained into how the microbe is able to survive its enzootic cycle and cause human disease. Here, we discuss the discovery of B. burgdorferi and its development as a model organism before diving into the critical lessons we have learned about B. burgdorferi biology at pivotal stages of its lifecycle: gene expression changes during the tick blood meal, colonization of a new vertebrate host, and developing a long-lasting infection in that vertebrate until a new tick feeds. Our goal is to highlight the advancements that have facilitated B. burgdorferi research and identify gaps in our current understanding of the microbe.