Senescence can be triggered by different kinds of stress. Cells can go through senescence in response to various stimuli, such as telomere shortening, alterations in telomeric structure, mitogenic indications, oncogenic stimulation, radiation, oxidative stress, epigenetic alterations, chromatin disorders, loss of proteostasis, mitochondrial dysfunction, inflammation, tissue damage, and nutrient deficiency. Senescence can also perform as an effective anti-tumor mechanism, by inhibiting proliferation of cancer cells during carcinogenesis. It is a cellular framework that exhibits both favorable and harmful effects on the health of an organism, a supposed instance of evolutionary antagonistic pleiotropy. Initiation of the p53/p21 WAF1/CIP1 and p16 INK4A /pRB tumor suppressing pathways, which is actuated in response to DNA damage produced by telomere attrition and oxidative or oncogenic stress, perform a key role in controlling senescence. Several other pathways have recently been associated with mediating senescence and the senescent phenotype. Better in-depth knowledge of the mechanisms regulating senescence may provide promising translational prospects to develop novel therapeutic strategies minimizing the harmful consequences of senescence. Targeting senescence by senolytic drugs to selectively eradicate senescent cells or control SASP using small molecules or antibodies will facilitate treatment of senescence related disorders and may contribute toward expanding healthspan.