Somatic cells are continuously exposed to stress from several endogenous and exogenous factors. Damaged cells can respond by undergoing a permanent cell cycle arrest termed cellular senescence. These senescent cells accumulate with age and are proposed to facilitate the development of aging phenotypes. In this chapter, we will review the processes involved in establishing cellular senescence and the different methods of detecting senescent cells in culture and in vivo. We will discuss how senescent cells can influence pathogenesis of many age-related diseases by eliciting a senescence-associated secretory phenotype (SASP). We will further describe the efforts being made to target senescent cells in humans as a therapeutic approach to treat age-related diseases.