In addition to common skin pathogens, acute focal lymphadenitis in humans can, in rare cases, be caused by a zoonotic pathogen. Furthermore, it can develop in the absence of any direct or indirect contact with infected animals, in cases when the microorganism is transmitted by a vector. These clinical entities are rare, and therefore often not easily recognized, yet many zoonotic illnesses are currently considered emerging or re-emerging in many regions. Focal zoonotic vector-borne lymphadenitis and its numerous causative agents, with their variegated clinical manifestations, have been described in some case reports and small case series. Therefore, we summarized those data in this narrative overview, with the aim of raising clinical awareness, which could improve clinical outcomes. This overview briefly covers reported pathogens, their vectors and geographic distribution, and their main clinical manifestations, diagnostic possibilities, and recommended therapy. Vector-borne tularemia, plague, bartonellosis, rickettsioses, borreliosis, and Malayan filariasis are mentioned. According to the existing data, when acute focal bacterial vector-borne zoonotic lymphadenitis is suspected, in severe or complicated cases it seems prudent to apply combined aminoglycoside (or quinolone) plus doxycycline as an empirical therapy, pending definite diagnostic results. In this field, the “one health approach” and further epidemiological and clinical studies are needed.