Mast cells, discovered over a century ago, have recently gained recognition for their crucial role in recognizing pathogens and modulating immune responses. Located at the host-environment interface, mast cells can instantaneously release pro-inflammatory mediators, making them essential for optimal immune responses during infections. They alter the inflammatory environment, mobilize immune cells to the site of infection, and to draining lymph nodes, with the timing and character of these responses varying based on the type of pathogen and the location of pathogen recognition. Mast cells are highly heterogeneous, with distinct subtypes and phenotypes that may influence their responses to different pathogens. They can be activated by various stimuli, including pattern recognition receptors (PRRs), Fc receptors (FcRs), and pathogen-associated substances. Mast cells can also undergo degranulation, releasing pre-packaged mediators, and produce cytokines and eicosanoids de novo. These responses help in recruiting immune cells, modulating the inflammatory environment, and promoting the function of antigen-specific lymphocytes. Mast cells play a significant role in innate and adaptive immune responses to parasites, bacteria, and viruses. They recruit immune cells, regulate gut permeability, and promote parasite expulsion. In bacterial infections, mast cells are essential for recruiting neutrophils and preventing dissemination. In viral infections, mast cells can promote CD8+ T cell recruitment and the production of type I interferons. Recent studies have shown that mast cell activators can enhance protective immunity during vaccination, suggesting the potential of using mast cells or their products as adjuvants. Mast cells' ability to orchestrate complex cellular migration and long-distance communication through exocytosed granules highlights their unique role in immune defense. Further research is needed to understand the functional contributions of mast cells in immunological memory and chronic infections.Mast cells, discovered over a century ago, have recently gained recognition for their crucial role in recognizing pathogens and modulating immune responses. Located at the host-environment interface, mast cells can instantaneously release pro-inflammatory mediators, making them essential for optimal immune responses during infections. They alter the inflammatory environment, mobilize immune cells to the site of infection, and to draining lymph nodes, with the timing and character of these responses varying based on the type of pathogen and the location of pathogen recognition. Mast cells are highly heterogeneous, with distinct subtypes and phenotypes that may influence their responses to different pathogens. They can be activated by various stimuli, including pattern recognition receptors (PRRs), Fc receptors (FcRs), and pathogen-associated substances. Mast cells can also undergo degranulation, releasing pre-packaged mediators, and produce cytokines and eicosanoids de novo. These responses help in recruiting immune cells, modulating the inflammatory environment, and promoting the function of antigen-specific lymphocytes. Mast cells play a significant role in innate and adaptive immune responses to parasites, bacteria, and viruses. They recruit immune cells, regulate gut permeability, and promote parasite expulsion. In bacterial infections, mast cells are essential for recruiting neutrophils and preventing dissemination. In viral infections, mast cells can promote CD8+ T cell recruitment and the production of type I interferons. Recent studies have shown that mast cell activators can enhance protective immunity during vaccination, suggesting the potential of using mast cells or their products as adjuvants. Mast cells' ability to orchestrate complex cellular migration and long-distance communication through exocytosed granules highlights their unique role in immune defense. Further research is needed to understand the functional contributions of mast cells in immunological memory and chronic infections.