Mitochondria, once viewed solely as energy producers, are now recognized as key regulators of innate immunity, influencing immune responses through their roles in energy production, signaling, and metabolic reprogramming. This review explores how mitochondrial physiology, including oxidative phosphorylation (OxPhos), mitochondrial nucleic acids, metabolites, and lipids, affects the functions of phagocytes such as macrophages and dendritic cells (DCs). These functions include macrophage polarization, efferocytosis, antibacterial activity, antigen presentation, immune signaling, and cytokine regulation. Proper regulation of these processes is essential for maintaining organismal homeostasis, and their disruption can lead to disease. Mitochondria are double-membraned organelles containing their own DNA (mtDNA), which is inherited matrilineally. They originated from an endosymbiotic event between an α-proteobacterium and an archaeon, and their dynamic nature has led to their role as central hubs in cellular signaling. Mitochondria are now understood to act as information processing systems, coordinating biosynthetic and signaling pathways. This concept is particularly relevant in innate immunity, where mitochondria contribute to immune responses through various mechanisms, including the production of reactive oxygen species (mtROS), mitochondrial DNA (mtDNA) signaling, and metabolic reprogramming. Mitochondrial bioenergetics, particularly OxPhos, is crucial for immune cell function. In macrophages, OxPhos is suppressed by NO production, leading to increased aerobic glycolysis and reduced inflammatory responses. Conversely, IL-4 stimulation enhances OxPhos, promoting anti-inflammatory responses. The NLRP3 inflammasome, a key player in innate immunity, is activated by mitochondrial-derived signals, including mtROS and mtDNA. These signals trigger pyroptosis and the release of pro-inflammatory cytokines such as IL-1β. Mitochondrial nucleic acid signaling, including mtDNA and mtRNA, plays a significant role in innate immunity. mtDNA can be recognized by TLR9, AIM2, and the cGAS-STING pathway, leading to the production of type I IFNs and pro-inflammatory cytokines. mtRNA, generated from mtDNA, can also trigger immune responses through RIG-I and MDA5. These signals are essential for detecting pathogens and initiating immune responses. Mitochondrial metabolite and lipid signaling, including the TCA cycle, also contribute to innate immunity. Metabolic reprogramming, such as the accumulation of succinate and itaconate, influences immune responses by modulating the stability of HIF-1α and the production of pro-inflammatory cytokines. Itaconate, a potent immunoregulatory metabolite, has anti-bacterial properties and can inhibit bacterial enzymes, contributing to host defense against intracellular pathogens. Overall, mitochondria are central to innate immunity, influencing immune responses through their roles in energy production, signaling, and metabolicMitochondria, once viewed solely as energy producers, are now recognized as key regulators of innate immunity, influencing immune responses through their roles in energy production, signaling, and metabolic reprogramming. This review explores how mitochondrial physiology, including oxidative phosphorylation (OxPhos), mitochondrial nucleic acids, metabolites, and lipids, affects the functions of phagocytes such as macrophages and dendritic cells (DCs). These functions include macrophage polarization, efferocytosis, antibacterial activity, antigen presentation, immune signaling, and cytokine regulation. Proper regulation of these processes is essential for maintaining organismal homeostasis, and their disruption can lead to disease. Mitochondria are double-membraned organelles containing their own DNA (mtDNA), which is inherited matrilineally. They originated from an endosymbiotic event between an α-proteobacterium and an archaeon, and their dynamic nature has led to their role as central hubs in cellular signaling. Mitochondria are now understood to act as information processing systems, coordinating biosynthetic and signaling pathways. This concept is particularly relevant in innate immunity, where mitochondria contribute to immune responses through various mechanisms, including the production of reactive oxygen species (mtROS), mitochondrial DNA (mtDNA) signaling, and metabolic reprogramming. Mitochondrial bioenergetics, particularly OxPhos, is crucial for immune cell function. In macrophages, OxPhos is suppressed by NO production, leading to increased aerobic glycolysis and reduced inflammatory responses. Conversely, IL-4 stimulation enhances OxPhos, promoting anti-inflammatory responses. The NLRP3 inflammasome, a key player in innate immunity, is activated by mitochondrial-derived signals, including mtROS and mtDNA. These signals trigger pyroptosis and the release of pro-inflammatory cytokines such as IL-1β. Mitochondrial nucleic acid signaling, including mtDNA and mtRNA, plays a significant role in innate immunity. mtDNA can be recognized by TLR9, AIM2, and the cGAS-STING pathway, leading to the production of type I IFNs and pro-inflammatory cytokines. mtRNA, generated from mtDNA, can also trigger immune responses through RIG-I and MDA5. These signals are essential for detecting pathogens and initiating immune responses. Mitochondrial metabolite and lipid signaling, including the TCA cycle, also contribute to innate immunity. Metabolic reprogramming, such as the accumulation of succinate and itaconate, influences immune responses by modulating the stability of HIF-1α and the production of pro-inflammatory cytokines. Itaconate, a potent immunoregulatory metabolite, has anti-bacterial properties and can inhibit bacterial enzymes, contributing to host defense against intracellular pathogens. Overall, mitochondria are central to innate immunity, influencing immune responses through their roles in energy production, signaling, and metabolic