Somatic cellular senescence (SCS) describes the limited ability of cells to divide. Normally, SCS is associated with physiological aging, but evidence suggests that it may play a role in disease progression, even in young patients. Stressors such as acute injury or chronic inflammation may induce SCS, which in turn exhausts organ regenerative potential. This review summarizes what is known about SCS in the kidney with aging and disease. As most patients with chronic kidney disease (CKD) also develop cardiovascular complications, a second focus of this review deals with the role of SCS in cardiovascular disease. Also, as SCS seems to accelerate CKD and cardiovascular disease progression, developing strategies for new treatment options that overcome SCS or protect a patient from it represents an exciting challenge.