Zoonotic infections, which are transmitted from animals to humans, have been a substantial source of human disease since antiquity. As the human population continues to grow and human influence on the planet expands, humans frequently encounter both domestic and wild animals. This has only increased as deforestation, urbanization, agriculture, habitat fragmentation, outdoor recreation, and international travel evolve in modern society, all of which have resulted in the emergence and reemergence of zoonotic infections. Zoonotic infections pose a diagnostic challenge because of their nonspecific clinical manifestations and the need for specialized testing procedures to confirm these diagnoses. Affected patients often undergo imaging during their evaluation, and a radiologist familiar with the specific and often subtle imaging patterns of these infections can add important clinical value. The authors review the multimodality thoracic, abdominal, and musculoskeletal imaging findings of zoonotic bacterial (eg, Bartonella henselae, Pasteurella multocida, Francisella tularensis, Coxiella burnetii, and Brucella species), spirochetal (eg, Leptospira species), and parasitic (eg, Echinococcus, Paragonimus, Toxocara, and Dirofilaria species) infections that are among the more commonly encountered zoonoses in the United States. Relevant clinical, epidemiologic, and pathophysiologic clues such as exposure history, occupational risk factors, and organism life cycles are also reviewed. Although many of the imaging findings of zoonotic infections overlap with those of nonzoonotic infections, granulomatous diseases, and malignancies, radiologists' familiarity with the imaging patterns can aid in the differential diagnosis in a patient with a suspected or unsuspected zoonotic infection. © RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.