Pattern recognition receptors (PRRs) are a class of receptors that can directly recognize specific molecular structures on the surface of pathogens, apoptotic host cells, and damaged senescent cells. PRRs bridge nonspecific immunity and specific immunity. Through the recognition and binding of ligands, PRRs can produce nonspecific anti-infection, antitumor, and other immunoprotective effects. Most PRRs in the innate immune system of vertebrates can be classified into five types based on protein domain homology: Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), C-type lectin receptors (CLRs), and absent in melanoma-2 (AIM2)-like receptors (ALRs). PRRs are composed of ligand recognition domains, intermediate domains, and effector domains. PRRs recognize and bind their respective ligands and recruit adaptor molecules with the same structure through their effector domains, initiating downstream signaling pathways to exert effects. Recent research on PRRs and their ligands has greatly promoted the understanding of PRR signaling pathways and provided ideas for the treatment of immune-related diseases and even tumors. This review describes the history, structural characteristics, ligand recognition mechanisms, signaling pathways, related diseases, new drugs in clinical trials, and clinical therapy of different types of PRRs. It discusses the significance of PRR research for the treatment of PRR-related diseases. PRRs are essential for innate immunity, recognizing pathogenic microorganisms and activating the expression of the second signal, which is indispensable for the activation of adaptive immunity. PRRs recognize PAMPs and DAMPs, which are essential for pathogen survival and usually have unique molecular or subcellular characteristics not found in host cells. PRRs can recognize these molecules, activate natural immunity, and cause inflammation. The study of PRR-mediated pattern recognition mechanisms helps elucidate signaling pathways and mechanisms of disease and provides new targets and methods for disease treatment. This review details the structural characteristics, ligand recognition mechanisms, signaling pathways, related diseases, new drugs in clinical trials, and clinical therapy of different types of PRRs. It focuses on the different domains and ligand recognition mechanisms between PRRs, which can provide new ideas for the definition, role, and clinical application of PRRs and promote the study of the role of the innate immune system in related diseases and even tumors.Pattern recognition receptors (PRRs) are a class of receptors that can directly recognize specific molecular structures on the surface of pathogens, apoptotic host cells, and damaged senescent cells. PRRs bridge nonspecific immunity and specific immunity. Through the recognition and binding of ligands, PRRs can produce nonspecific anti-infection, antitumor, and other immunoprotective effects. Most PRRs in the innate immune system of vertebrates can be classified into five types based on protein domain homology: Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), C-type lectin receptors (CLRs), and absent in melanoma-2 (AIM2)-like receptors (ALRs). PRRs are composed of ligand recognition domains, intermediate domains, and effector domains. PRRs recognize and bind their respective ligands and recruit adaptor molecules with the same structure through their effector domains, initiating downstream signaling pathways to exert effects. Recent research on PRRs and their ligands has greatly promoted the understanding of PRR signaling pathways and provided ideas for the treatment of immune-related diseases and even tumors. This review describes the history, structural characteristics, ligand recognition mechanisms, signaling pathways, related diseases, new drugs in clinical trials, and clinical therapy of different types of PRRs. It discusses the significance of PRR research for the treatment of PRR-related diseases. PRRs are essential for innate immunity, recognizing pathogenic microorganisms and activating the expression of the second signal, which is indispensable for the activation of adaptive immunity. PRRs recognize PAMPs and DAMPs, which are essential for pathogen survival and usually have unique molecular or subcellular characteristics not found in host cells. PRRs can recognize these molecules, activate natural immunity, and cause inflammation. The study of PRR-mediated pattern recognition mechanisms helps elucidate signaling pathways and mechanisms of disease and provides new targets and methods for disease treatment. This review details the structural characteristics, ligand recognition mechanisms, signaling pathways, related diseases, new drugs in clinical trials, and clinical therapy of different types of PRRs. It focuses on the different domains and ligand recognition mechanisms between PRRs, which can provide new ideas for the definition, role, and clinical application of PRRs and promote the study of the role of the innate immune system in related diseases and even tumors.