An altered gut microbiome is a feature of many multifactorial diseases, and microbiome effects on host metabolism, immune function, and possibly neurological function are implicated. Increased biological age is accompanied by a change in the gut microbiome. However, age-related health loss does not occur uniformly across all subjects but rather depends on differential loss of gut commensals and gain of pathobionts. In this article, we summarize the known and possible effects of the gut microbiome on the hallmarks of aging and describe the most plausible mechanisms. Understanding and targeting these factors could lead to prolonging health span by rationally maintaining the gut microbiome.