In the first paper of the special issue, “Epigenetic regulation of apoptosis and cell cycle in osteosarcoma,” Kleinerman and K. Rao-Bindal critically discuss frequency and prognostic impact of epigenetic inactivation of p16/p14ARF, HIC1, and RASSF1A in this disease, as well as the possible role of histone H3 lysine 27 monomethylation in osteosarcoma apoptosis. Here, CDKN2A is linked to osteosarcoma.