There have been strange couples throughout history, which have behaved in an opposite manner while sharing the same space, with, in our opinion, Jack Lemon and Walter Matthau (the "Odd Couple") being one of the best examples. Most biological processes are interconnected with each other, and the imbalance in favor of one or another always involves biological changes. In the case of cell death by genotoxic stress, there are two main actors who seem to have a decisive role: apoptosis and autophagy. We have recently shown how a MAPK signaling pathway, the p38 pathway, may be controlling the balance of both processes in genotoxic stress conditions triggered by a therapeutic agent commonly used in cancer therapy such as 5-fluorouracil.