Toll-like receptors (TLRs) have emerged as major receptor components of pattern-recognition receptors (PRRs), which are responsible for the recognition of pathogen-associated molecular patterns (PAMPs)-derived pathogenic parasites. This recognition triggers the secretion of a large amount of type I interferons (IFNs), inflammatory cytokines, and chemokines and maturation of immune cells, for effective host defense by eradicating infectious parasites. Both the myeloid differentiation factor 88 (MyD88) and the TIR domain containing the adaptor molecule (TRIF) are involved in these signaling pathways. Here, we review the latest ?ndings on the recognition of the pathogenic parasites and activation of corresponding signaling pathways through TLRs, with special emphasis on the recognition of pathogenic protozoan and helminthes. By highlighting recent progress in these areas, we hope to provide references in future studies not only for the complexity of host-parasite interactions but also for the prevention of the pathogenic parasite infections.