Cellular senescence, a stress response that stabilizes and blocks proliferation, is increasingly recognized as a critical component in cancer prevention. Senescence is prevalent in premalignant tumors, and progression to malignancy often involves evading senescence. However, malignant tumors can still undergo senescence through interventions that restore tumor suppressors or inactivate oncogenes. Senescent tumor cells can be cleared by immune cells, leading to efficient tumor regression. Standard chemotherapy also has the potential to induce senescence, which may contribute to its therapeutic activity. While these concepts are well-supported in mouse models, translating them to clinical oncology remains challenging. The initial description of cellular senescence was based on the analysis of normal human cells grown in vitro, where Hayflick and collaborators found that normal cells have a finite proliferative capacity that ends in a stable and long-term cell cycle arrest. This response is now understood to involve multiple mechanisms, including telomere shortening, upregulation of the CDKN2A locus, and accumulation of DNA damage. Oncogene-induced senescence (OIS) emerged as a putative tumor suppressor mechanism, similar to oncogene-induced apoptosis. Studies in mouse models have shown that oncogenic Ras, Raf/Mek pathway, and other oncogenes can trigger senescence in premalignant tumors. For example, endogenous *Kras*^G12V^ in lung and pancreatic tumors, *Braf*^V600E^ in melanocytic nevi, and *Nras*^G12D^ in lymphoid tissue have all been linked to senescence. Senescence is characteristic of premalignant stages of tumor development but is absent in malignant stages. This suggests that senescence acts as a barrier to tumor progression. Tumor suppressors like p53, INK4A, and ARF monitor oncogenic signaling and trigger senescence when activated. However, other tumor suppressors like PTEN, VHL, NF1, and RB function upstream of oncogenes, preventing excessive proliferative signaling. The levels of oncogene activity determine the outcome of senescence. Low levels of oncogenic expression are often inconsequential, while high levels can lead to premalignant tumors and senescence. Senescence-inducing therapies, such as restoring p53 function or inactivating oncogenes, have shown promise in mouse models and human studies, suggesting their potential as anti-cancer treatments. However, caution is needed, as senescent tumor cells can remain dormant and potentially relapse. Additionally, senescent cells release pro-inflammatory cytokines and may stimulate malignant phenotypes of nearby tumor cells. Despite these challenges, the potential of senescence-inducing therapies in cancer treatment is promising, and further research is needed to optimize their use.Cellular senescence, a stress response that stabilizes and blocks proliferation, is increasingly recognized as a critical component in cancer prevention. Senescence is prevalent in premalignant tumors, and progression to malignancy often involves evading senescence. However, malignant tumors can still undergo senescence through interventions that restore tumor suppressors or inactivate oncogenes. Senescent tumor cells can be cleared by immune cells, leading to efficient tumor regression. Standard chemotherapy also has the potential to induce senescence, which may contribute to its therapeutic activity. While these concepts are well-supported in mouse models, translating them to clinical oncology remains challenging. The initial description of cellular senescence was based on the analysis of normal human cells grown in vitro, where Hayflick and collaborators found that normal cells have a finite proliferative capacity that ends in a stable and long-term cell cycle arrest. This response is now understood to involve multiple mechanisms, including telomere shortening, upregulation of the CDKN2A locus, and accumulation of DNA damage. Oncogene-induced senescence (OIS) emerged as a putative tumor suppressor mechanism, similar to oncogene-induced apoptosis. Studies in mouse models have shown that oncogenic Ras, Raf/Mek pathway, and other oncogenes can trigger senescence in premalignant tumors. For example, endogenous *Kras*^G12V^ in lung and pancreatic tumors, *Braf*^V600E^ in melanocytic nevi, and *Nras*^G12D^ in lymphoid tissue have all been linked to senescence. Senescence is characteristic of premalignant stages of tumor development but is absent in malignant stages. This suggests that senescence acts as a barrier to tumor progression. Tumor suppressors like p53, INK4A, and ARF monitor oncogenic signaling and trigger senescence when activated. However, other tumor suppressors like PTEN, VHL, NF1, and RB function upstream of oncogenes, preventing excessive proliferative signaling. The levels of oncogene activity determine the outcome of senescence. Low levels of oncogenic expression are often inconsequential, while high levels can lead to premalignant tumors and senescence. Senescence-inducing therapies, such as restoring p53 function or inactivating oncogenes, have shown promise in mouse models and human studies, suggesting their potential as anti-cancer treatments. However, caution is needed, as senescent tumor cells can remain dormant and potentially relapse. Additionally, senescent cells release pro-inflammatory cytokines and may stimulate malignant phenotypes of nearby tumor cells. Despite these challenges, the potential of senescence-inducing therapies in cancer treatment is promising, and further research is needed to optimize their use.