Pattern recognition receptors (PRRs) are a class of receptors that recognize specific molecular structures on the surfaces of pathogens, apoptotic host cells, and damaged senescent cells. They bridge nonspecific immunity and specific immunity by producing anti-infection, antitumor, and other immunoprotective effects. PRRs 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). These receptors are composed of ligand recognition domains, intermediate domains, and effector domains. They recognize and bind their respective ligands, recruit adaptor molecules, and initiate downstream signaling pathways to exert effects. The recognition and binding of PRRs to their ligands are critical in initiating the innate immune response. Recent research has significantly advanced the understanding of different PRR signaling pathways and provided insights for the treatment of immune-related diseases and even tumors. This review covers the history, structural characteristics, ligand recognition mechanisms, signaling pathways, related diseases, new drugs in clinical trials, and clinical therapies of different types of PRRs. It also discusses the significance of studying pattern recognition mechanisms for treating PRR-related diseases. PRRs play a crucial role in innate immunity, which is divided into two levels: physical barriers and the innate immune system. The innate immune system includes monocytes, neutrophils, macrophages, dendritic cells, natural killer (NK) cells, mast cells, eosinophils, and basophils. Unlike T cells and B cells, which have high specificity, these innate immune cells do not express specific antigen recognition receptors. Instead, they recognize common molecules on the surfaces of pathogens, apoptotic host cells, and damaged senescent cells, inducing immunoprotective effects such as anti-infection and antitumor effects. The discovery of PRRs and their ligands has been epoch-making, connecting the innate immune signal to the initiation of adaptive immune responses. PRRs can recognize pathogenic microorganisms and activate the second signal required to activate T cells, thereby controlling adaptive immunity. TLRs, one of the earliest discovered PRRs, play a significant role in inflammatory responses. The development history of PRRs, particularly TLRs, is briefly described, highlighting their structure, function, and signaling pathways. TLRs are membrane-bound signal receptors that recognize PAMPs through leucine-rich repeats (LRRs) and transmit signals via Toll/IL-1R (TIR) domains. They can be divided into MyD88-dependent and MyD88-independent pathways. TLRs recognize different subcellular structures, with some expressed on the surface of immune cells and others in thePattern recognition receptors (PRRs) are a class of receptors that recognize specific molecular structures on the surfaces of pathogens, apoptotic host cells, and damaged senescent cells. They bridge nonspecific immunity and specific immunity by producing anti-infection, antitumor, and other immunoprotective effects. PRRs 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). These receptors are composed of ligand recognition domains, intermediate domains, and effector domains. They recognize and bind their respective ligands, recruit adaptor molecules, and initiate downstream signaling pathways to exert effects. The recognition and binding of PRRs to their ligands are critical in initiating the innate immune response. Recent research has significantly advanced the understanding of different PRR signaling pathways and provided insights for the treatment of immune-related diseases and even tumors. This review covers the history, structural characteristics, ligand recognition mechanisms, signaling pathways, related diseases, new drugs in clinical trials, and clinical therapies of different types of PRRs. It also discusses the significance of studying pattern recognition mechanisms for treating PRR-related diseases. PRRs play a crucial role in innate immunity, which is divided into two levels: physical barriers and the innate immune system. The innate immune system includes monocytes, neutrophils, macrophages, dendritic cells, natural killer (NK) cells, mast cells, eosinophils, and basophils. Unlike T cells and B cells, which have high specificity, these innate immune cells do not express specific antigen recognition receptors. Instead, they recognize common molecules on the surfaces of pathogens, apoptotic host cells, and damaged senescent cells, inducing immunoprotective effects such as anti-infection and antitumor effects. The discovery of PRRs and their ligands has been epoch-making, connecting the innate immune signal to the initiation of adaptive immune responses. PRRs can recognize pathogenic microorganisms and activate the second signal required to activate T cells, thereby controlling adaptive immunity. TLRs, one of the earliest discovered PRRs, play a significant role in inflammatory responses. The development history of PRRs, particularly TLRs, is briefly described, highlighting their structure, function, and signaling pathways. TLRs are membrane-bound signal receptors that recognize PAMPs through leucine-rich repeats (LRRs) and transmit signals via Toll/IL-1R (TIR) domains. They can be divided into MyD88-dependent and MyD88-independent pathways. TLRs recognize different subcellular structures, with some expressed on the surface of immune cells and others in the