Monocytes are essential for immune defense against microbial pathogens by supplying macrophage and dendritic cell (DC) precursors to peripheral tissues and directly contributing to immune responses. In humans and mice, monocytes are divided into two major subsets: CD14⁺ monocytes, which are large and constitutively maintain tissue macrophage/DC populations, and CD16⁺ monocytes, which are smaller and respond to microbial stimuli by secreting cytokines and antimicrobial factors. Inflammatory monocytes, which express CCR2 and respond to monocyte chemoattractant protein (MCP-1), are crucial for defense against bacterial, protozoal, and fungal pathogens. Monocyte recruitment to sites of infection involves CCR2-mediated emigration from the bone marrow, followed by trafficking into infected tissues. Recent studies highlight the complexity of this process, involving chemokine secretion, monocyte differentiation, and microbial killing. Monocytes can differentiate into DCs, tissue macrophages, and other immune cells, playing a key role in immune responses. In the context of infections such as Listeria monocytogenes, Mycobacterium tuberculosis, Toxoplasma gondii, and Cryptococcus neoformans, monocytes are essential for pathogen clearance. Monocyte subsets, such as Ly6C⁺ and CX3CR1⁺ monocytes, have distinct roles in immune defense, with Ly6C⁺ monocytes being inflammatory and CX3CR1⁺ monocytes being resident. Monocytes contribute to immune responses by producing reactive nitrogen intermediates (RNI), reactive oxygen intermediates (ROI), and antimicrobial factors. Chemokines such as MCP-1 and CCR2 are critical for monocyte recruitment and immune control. Monocyte recruitment is essential for host defense against various pathogens, and defects in this process can lead to increased susceptibility to infections. Overall, monocytes play a vital role in immune defense by contributing to the initiation and regulation of immune responses against microbial pathogens.Monocytes are essential for immune defense against microbial pathogens by supplying macrophage and dendritic cell (DC) precursors to peripheral tissues and directly contributing to immune responses. In humans and mice, monocytes are divided into two major subsets: CD14⁺ monocytes, which are large and constitutively maintain tissue macrophage/DC populations, and CD16⁺ monocytes, which are smaller and respond to microbial stimuli by secreting cytokines and antimicrobial factors. Inflammatory monocytes, which express CCR2 and respond to monocyte chemoattractant protein (MCP-1), are crucial for defense against bacterial, protozoal, and fungal pathogens. Monocyte recruitment to sites of infection involves CCR2-mediated emigration from the bone marrow, followed by trafficking into infected tissues. Recent studies highlight the complexity of this process, involving chemokine secretion, monocyte differentiation, and microbial killing. Monocytes can differentiate into DCs, tissue macrophages, and other immune cells, playing a key role in immune responses. In the context of infections such as Listeria monocytogenes, Mycobacterium tuberculosis, Toxoplasma gondii, and Cryptococcus neoformans, monocytes are essential for pathogen clearance. Monocyte subsets, such as Ly6C⁺ and CX3CR1⁺ monocytes, have distinct roles in immune defense, with Ly6C⁺ monocytes being inflammatory and CX3CR1⁺ monocytes being resident. Monocytes contribute to immune responses by producing reactive nitrogen intermediates (RNI), reactive oxygen intermediates (ROI), and antimicrobial factors. Chemokines such as MCP-1 and CCR2 are critical for monocyte recruitment and immune control. Monocyte recruitment is essential for host defense against various pathogens, and defects in this process can lead to increased susceptibility to infections. Overall, monocytes play a vital role in immune defense by contributing to the initiation and regulation of immune responses against microbial pathogens.