Mesquite (Prosopis juliflora (Sw.) DC), is an medium-sized tree (family Fabaceae, subfamily Mimosoideae), that has been intorcuded around the world. It is a noxious invasive species in Africa, Asia, and the Arabian Peninsula and a source of highly allergenic pollen in. The present article reviews the adverse allergenic effects of P. juliflora pollen on human and animal health. Several studies have diagnosed that allergenic pollens from Prosopis spp. can provoke respiratory problems. Prosopis pollen extracts have 16 allergenic components of which nine proteins were recognized as major allergens with some of them showing cross-reactivity. Clinically, understanding Prosopis pollen production, flowering seasonality, pollen load, and dispersal in the atmosphere are important to avoid allergic consequences for local inhabitants. Climate change and other pollution can also help to further facilitate allergenic issues. Furthermore, we document other human and animal health problems caused by invasive Prosopis trees. This includes flesh injuries, dental and gastric problems, and the facilitation of malaria. This review summarizes and enhances the existing knowledge about Prosopis flowering phenology, aeroallergen, and other human and animal health risks associated with this noxious plant.