Human immune system aging results in impaired responses to pathogens or vaccines. In the innate immune system, which mediates the earliest pro-inflammatory responses to immunologic challenge, processes ranging from Toll-like Receptor function to Neutrophil Extracellular Trap formation are generally diminished in older adults. Dysregulated, enhanced basal inflammation with age reflecting activation by endogenous damage-associated ligands contributes to impaired innate immune responses. In the adaptive immune system, T and B cell subsets and function alter with age. The control of cytomegalovirus infection, particularly in the T lineage, plays a dominant role in the differentiation and diversity of the T cell compartment.