Purpose of Review <p>Fleas (order Siphonaptera) are hematophagous ectoparasites distributed worldwide that parasitize wild, synanthropic, and domestic birds and mainly mammals. Beyond their role as infestation agents, fleas act as vectors of zoonotic pathogens of public health importance. This review synthesizes current knowledge on the ecology and epidemiology of the main flea-borne diseases in the Americas from a One Health perspective.</p> Recent Findings <p>In the Americas, fleas can cause direct parasitism, such as the case of tungiasis, or can be biological vectors of some infectious diseases including murine typhus, flea-borne spotted fever, bartonellosis, and plague. These conditions persist in heterogeneous ecological contexts ranging from sylvatic cycles to densely populated urban environments. Transmission dynamics are shaped by host–vector networks, landscape connectivity, and socioenvironmental determinants. Evidence indicates that flea-borne pathogens operate within interconnected ecological networks structured by host community composition, habitat fragmentation, and anthropogenic landscape transformation. Despite advances in molecular detection and ecological characterization, significant gaps remain in integrated surveillance, comparative analyses across flea-borne pathogens, and understanding of landscape processes influencing spillover risk.</p> Summary <p>Strengthening interdisciplinary and One Health approaches is essential to improve prevention strategies, early detection, and control of flea-associated zoonoses in the Americas.</p>