The article reviews the mechanisms underlying immunosuppression by regulatory cells, including regulatory T cells (Tregs), regulatory B cells (Bregs), and myeloid-derived suppressor cells (MDSCs). These cells play crucial roles in maintaining immune tolerance and controlling immune responses during infections to prevent excessive activation. However, pathogens have evolved strategies to hijack these regulatory cells, reducing the overall effectiveness of the immune response. Therapeutic targeting of these immunosuppressive mechanisms can enhance the immune response and improve infection outcomes. The suppressive mechanisms of regulatory cells are numerous and redundant, reflecting the complexity of the regulatory network. Context-specific factors, such as the type of pathogen or tissue involved, influence the regulatory mechanisms. Key mechanisms include the production of inhibitory cytokines like IL-10 and TGF-β, which inhibit pro-inflammatory cytokine production and effector T cell activation. Regulatory cells also use inhibitory receptors like CTLA-4 and PD-1 to suppress effector cells. Additionally, metabolic reprogramming in effector immune cells is another modality of immunosuppression. The article provides an overview of the major mechanisms mediating the immunosuppressive effects of different regulatory cell subsets in the context of infection.The article reviews the mechanisms underlying immunosuppression by regulatory cells, including regulatory T cells (Tregs), regulatory B cells (Bregs), and myeloid-derived suppressor cells (MDSCs). These cells play crucial roles in maintaining immune tolerance and controlling immune responses during infections to prevent excessive activation. However, pathogens have evolved strategies to hijack these regulatory cells, reducing the overall effectiveness of the immune response. Therapeutic targeting of these immunosuppressive mechanisms can enhance the immune response and improve infection outcomes. The suppressive mechanisms of regulatory cells are numerous and redundant, reflecting the complexity of the regulatory network. Context-specific factors, such as the type of pathogen or tissue involved, influence the regulatory mechanisms. Key mechanisms include the production of inhibitory cytokines like IL-10 and TGF-β, which inhibit pro-inflammatory cytokine production and effector T cell activation. Regulatory cells also use inhibitory receptors like CTLA-4 and PD-1 to suppress effector cells. Additionally, metabolic reprogramming in effector immune cells is another modality of immunosuppression. The article provides an overview of the major mechanisms mediating the immunosuppressive effects of different regulatory cell subsets in the context of infection.