Lyme disease is the most common vector-transmitted illness in the USA and Europe. The pathogen, Borrelia burgdorferi, causes a complex spectrum of disease that affects the skin, joints, nervous system and heart. Patients in the early stages of the disease can often be successfully treated with antibiotics but this becomes less reliable as the disease progresses. The specific immune responses that are detectable in patients with Lyme disease are not sufficient to protect against illness; a vaccine against the infectious agent is, therefore, desirable. In this article Markus M. Simon and colleagues present a mouse model of Borrelia burgdorferi infection. Their work suggests that the outer surface protein A (OspA) of Borrelia burgdorferi may be a suitable vaccine candidate.