By focusing on the pioneering MDM2 inhibitor Nutlin-3a, which dislodges the E3 ubiquitin ligase MDM2 from p53 (32) and thus promises to be a powerful anti-cancer agent for patients with wild-type (WT) p53 (33), we show that selective perturbation of P-TEFb converts the fate of Nutlin-3a-treated cells from cell-cycle arrest to apoptosis. The gene discussed is TP53; the disease is cancer.