Despite the enormous, global scale of cancer, it is fundamentally a genetic disease whose underlying mechanisms require an understanding of the disease at the subcellular and molecular scale. Cancer research has undergone an explosion of new knowledge in recent decades spurred on by relatively recent advances in DNA sequencing and whole genome sequencing. The daunting complexity of the ever-expanding body of knowledge defies comprehension, but has been simplified by the hallmarks of cancer framework. Cancer development and progression entails stepwise attainment of traits that allow it to behave like cancer. These skills include mitogenic self-sufficiency, insensitivity to growth suppression, limitless replicative ability, evasion of the immune system, reprogramming metabolism, sustained angiogenesis, evasion of death, invasion and metastasis, and two enabling characteristics. These skills together give the cell the ability to behave like cancer cells and cause disease. Insights into the molecular mechanisms of malignant transformation and progression have revolutionized the development of novel diagnostic and therapeutic modalities and introduced entirely new classes of cancer drugs with better specificity, lower side effects, and better outcomes.