Elderly individuals display increased susceptibility to chronic inflammatory diseases and microbial infections, such as periodontitis and oral aspiration pneumonia. The resurgent interest in innate immunity in the 2000s has been accompanied by parallel studies to understand the impact of aging on the function of the innate immune system, which not only provides first-line defense but is essential for the development of adaptive immunity. This review summarizes and discusses our current understanding of age-associated molecular alterations in neutrophils and macrophages, key inflammatory phagocytes implicated in both protective and destructive host responses. The analysis of recent literature suggests that, in advanced age, phagocytes undergo significant changes in signal transduction pathways that may affect their ability to perform antimicrobial functions or regulate the inflammatory response. These abnormalities are expected to contribute to the pathology of oral infection-driven inflammatory diseases in the elderly. Moreover, the elucidation of age-associated defects in the innate immune system will facilitate the development of intervention therapeutic strategies to promote or restore innate immune function and improve the quality of health in old age.