Cellular senescence is a state of permanent cell cycle arrest, which has been shown to prevent neoplastic transformation. Oncogenes are pro-proliferative genes that promote survival and proliferation of cancer cells. Paradoxically, introduction of an activated oncogene leads to activation of a state similar to cellular senescence, which is referred to as oncogene-induced senescence. Studies have shown that oncogene-induced senescence function as a barrier to neoplastic transformation. Here, we describe a protocol for inducing cellular senescence by oncogenic RAS in primary human fibroblast. The approach that we describe here is of general utility and can be applied to study senescence induction by other defined genetic elements, for example, other activated oncogenes. © Springer Science+Business Media, New York 2013.