Arising from an initiative by the National Institute of Aging (NIA) requesting novel proposals challenged with increasing lifespan and longevity, our laboratory has generated a hypothesis to test the efficacy of lifelong, low-dosage aspirin administration as a means to achieving this goal. The intervention testing program (currently underway) proposing aspirin as an anti-aging agent evolved from the multitude of properties encompassed in aspirin and the potential of these attributes to prevent the cellular and functional declines, particularly from inflammatory and oxidative sources, evidenced to contribute to aging. Aspirin is a widely administered, cheap, anti-inflammatory, and antioxidant compound that has a variety of positive effects on the immune system and cardiovascular health. Notably, aspirin may affect oxidant production, cytokine responses, and block glycooxidation reactions, thus posing it as a triple threat against the symptoms of aging. Whether aging is molded by interplay between oxidative stress and inflammatory mediators has received little attention; however, we and other laboratories have explored this notion and have observed an elevated inflammatory status with age. Stemming from these observations and in view of the limited success of antioxidant therapies in improving lifespan in long-lived species, in this article we propose a protocol to examine life-long use of a very low dose anti-inflammatory compound such as aspirin to engage the inflammatory and endogenous oxidative insults accompanying aging and, in so doing, attempt to increase maximum and mean life span.