Genome modifications resulting from epigenetic changes appear to play a critical role in the development and/or progression of cancer. Scatter experimental evidence suggests that epigenetic changes could also be critical determinants of cellular senescence and organismal aging. Here we review the current evidence and discuss how imbalances in chromatin remodelers might trigger irreversible growth arrest in proliferating cells and tissues. Experimental data using drugs that target specific chromatin remodeling enzymes suggest that such approach could lead to the development of novel therapeutic modalities for the prevention or amelioration of some age-related dysfunctions.