Plasmacytoid dendritic cells (pDCs) are a unique subset of dendritic cells specialized in producing type I interferons (IFNs). They play a critical role in antiviral immunity and have been implicated in autoimmune diseases with a type I IFN signature. However, pDCs can also induce tolerogenic immune responses. This review summarizes recent advances in pDC biology, focusing on their development, functions, pathogen sensing, mucosal roles, and involvement in infections, autoimmunity, and cancer. pDCs express markers such as BDCA2 and ILT7, and their development is regulated by transcription factors like E2-2 and signaling pathways involving FLT3, STAT3, and STAT5. pDCs recognize pathogens and self-nucleic acids via TLR7 and TLR9, leading to IFN production and pro-inflammatory cytokine secretion. They also present antigens to CD4+ T cells and can induce tolerance. pDCs are crucial in viral infections, where they produce IFN to control viral replication, but excessive IFN can cause inflammation. In chronic infections like HIV, pDCs contribute to disease progression through dysregulated IFN production and activation. In autoimmune diseases such as SLE, pDCs are involved in disease pathogenesis through IFN production and immune complex activation. pDCs in the gut and mucosal tissues play roles in immune regulation, tolerance, and B cell responses. Overall, pDCs are multifaceted cells with diverse functions in immunity and disease.Plasmacytoid dendritic cells (pDCs) are a unique subset of dendritic cells specialized in producing type I interferons (IFNs). They play a critical role in antiviral immunity and have been implicated in autoimmune diseases with a type I IFN signature. However, pDCs can also induce tolerogenic immune responses. This review summarizes recent advances in pDC biology, focusing on their development, functions, pathogen sensing, mucosal roles, and involvement in infections, autoimmunity, and cancer. pDCs express markers such as BDCA2 and ILT7, and their development is regulated by transcription factors like E2-2 and signaling pathways involving FLT3, STAT3, and STAT5. pDCs recognize pathogens and self-nucleic acids via TLR7 and TLR9, leading to IFN production and pro-inflammatory cytokine secretion. They also present antigens to CD4+ T cells and can induce tolerance. pDCs are crucial in viral infections, where they produce IFN to control viral replication, but excessive IFN can cause inflammation. In chronic infections like HIV, pDCs contribute to disease progression through dysregulated IFN production and activation. In autoimmune diseases such as SLE, pDCs are involved in disease pathogenesis through IFN production and immune complex activation. pDCs in the gut and mucosal tissues play roles in immune regulation, tolerance, and B cell responses. Overall, pDCs are multifaceted cells with diverse functions in immunity and disease.