Cat-scratch disease has been recognized since 1889 in association with the oculoglandular syndrome of Parinaud. The epidemiologic association with cats was first made in 1931 and further substantiated throughout the years, refining the interaction predominantly to kittens. Putative infectious agents have included numerous species of bacteria, chlamydiae, and viruses. The cultivation of Afipia spp. in the late 1980s appeared to answer the mystery of the identity of the agent. However, even more recent analysis, which has combined traditional microbiology, molecular methods, and additional epidemiology, has demonstrated that Bartonella (Rochalimaea) henselae is the definitive agent of cat-scratch disease. Our understanding of the pathogenesis of cat-scratch disease and other diseases caused by Bartonella species is incomplete and the spectrum of diseases continues to emerge. We review historic and modern efforts to understand the etiology of cat-scratch disease and related syndromes.