Cellular senescence is a program activated by normal cells in response to 
various types of stress. These include telomere uncapping, DNA damage, oxidative 
stress, oncogene activity and others. Senescence can occur following a period of 
cellular proliferation or in a rapid manner in response to acute stress. Once 
cells have entered senescence, they cease to divide and undergo a series of 
dramatic morphologic and metabolic changes. Cellular senescence is thought to 
play an important role in tumor suppression and to contribute to organismal 
aging, but a detailed description of its physiologic occurrence in vivo is 
lacking. Recent studies have provided important insights regarding the manner by 
which different stresses and stimuli activate the signaling pathways leading to 
senescence. These studies reveal that a population of growing cells may suffer 
from a combination of different physiologic stresses acting simultaneously. The 
signaling pathways activated by these stresses are funneled to the p53 and Rb 
proteins, whose combined levels of activity determine whether cells enter 
senescence. Here we review recent advances in our understanding of the stimuli 
that trigger senescence, the molecular pathways activated by these stimuli, and 
the manner by which these signals determine the entry of a population of cells 
into senescence.