The integrity of the chromatin associated with telomeric regions, which include telomeres and subtelomeres, is essential for telomeres function and cell viability. Whereas human subtelomeres are heterochromatic, telomeres are labeled with euchromatic marks like H4K20me1 and H3K27ac in most commonly studied human cell lines. The epigenetic marks of human telomeric regions influence oncogenic processes. Indeed, different drugs that decrease their genome-wide levels are currently being used or tested in specific cancer therapies. These drugs can challenge cancer by altering the function of key cellular proteins. However, they should also compromise oncogenic processes by modifying the epigenetic landscape of telomeric regions. We believe that studies of telomeric chromatin structure and telomeres dysfunction should help to design epigenetic therapies for cancer treatment.