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The innate immune system is responsible for initial control of pathogens by directly eliminating infections, engaging nearby cells, and recruiting adaptive immune cells. In contrast to the adaptive immune system, which requires training and is exquisitely specific to particular pathogens, the innate immune system senses and responds to numerous infections directly. The innate immune system is composed of multiple cell types with distinct critical functions both in the circulation and following infiltration into tissues to provide early responses to infection or injury. Innate immune cells such as neutrophils and monocytes circulate throughout the body and are capable of rapidly infiltrating tissues; macrophages and dendritic cells (DCs) reside within tissue and have important roles in tissue surveillance and antigen presentation. Innate immune cells rely on a variety of pattern recognition receptors (PRRs) to sense tissue disturbance and also recognize pathogenic invasion. Membrane-associated Toll-like receptors (TLRs) on the cell surface and within endosomes sense diverse structural patterns associated with pathogens such as lipoproteins, lipopolysaccharide, flagellin, and nucleic acids. Numerous studies have reported diminished responsiveness to TLR ligands in innate immune cells from elderly donors as compared to younger donors and are discussed in more detail in the sections below. Nod-like receptors and retinoic acid-inducible gene-I (RIG-I)-like receptors are cytosolic sensors that respond to bacterial or viral molecular components to initiate inflammatory responses that limit pathogen spread. While aging affects each of these cell types and functional responses differently, some unifying mechanistic alterations offer insights to immune dysfunction in aging.