The past decade has been marked by an explosion of knowledge regarding the dysregulation of cancer at the molecular level. It has become apparent that oncogenes, tumor suppressor genes, and other ancillary molecules interact in complex pathways that govern cellular homeostasis. We review three molecular events that have been implicated in tumorigenesis and define pathways ripe for the development of new therapeutic approaches: 1) activation of telomerase, 2) dysregulation of the patched/sonic hedgehog pathway, and 3) mutation of the INK4 alpha-ARF locus.