Clonal hematopoiesis (CH) has been associated with aging, occurring in about 10% of individuals aged >70 years, and immune dysfunction. Aged hematopoietic stem and progenitor cells exhibit pathological changes in immune function and activation of inflammatory pathways. CH clones commonly harbor a loss of function mutation in DNMT3A or TET2, which causes increased expression of inflammatory signaling genes, a proposed mechanism connected to CH and the development of age-related diseases. Additionally, inflammation may stress the hematopoietic compartment, driving the expansion of mutant clones. While the epidemiologic overlap between CH, hematologic malignancies, and atherosclerotic cardiovascular diseases has been reported, the mechanisms linking these concepts are largely unknown and merit much further investigation. Here, we review studies highlighting the interplay between CH, inflamm-aging, the immune system, and the prevalence of CH in autoimmune diseases.