Aging is characterized by the accumulation of damage and other deleterious changes, leading to the loss of functionality and fitness. Age-related changes occur at most levels of organization of a living organism (molecular, organellar, cellular, tissue and organ). However, protein synthesis is a major biological process, and thus understanding how it changes with age is of paramount importance. Here, we discuss the relationships between lifespan, aging, protein synthesis and translational control, and expand this analysis to the various aspects of proteome behavior in organisms with age. Characterizing the consequences of changes in protein synthesis and translation fidelity, and determining whether altered translation is pathological or adaptive is necessary for understanding the aging process, as well as for developing approaches to target dysfunction in translation as a strategy for extending lifespan.