We review and discuss here evidence for Myc-induced senescence - which is detectable to a limited degree as a cell-autonomous, direct response to Myc action, but occurs predominantly in a non-cell-autonomous fashion via crosstalk of the oncogene-driven cell population with non-neoplastic bystanders, namely cells of the host immune system, prompting them to release pro-senescent cytokines that strike back onto adjacent proliferating tumor cells.