Late effects are prolonged health effects that are absent or subclinical during the treatment period and that manifest after the end of the treatment responsible for the health effect. Long-term effects are prolonged health effects that manifest during the treatment responsible for the health effect and continues after discontinuation of treatment. This chapter addresses some of the most serious physical late and long-term effects. A steady increase in cancer survivorship during recent decades has surpassed increases in incidence of many chronic conditions including peptic ulcer disease, coronary artery disease (CAD), stroke, chronic obstructive pulmonary disease, and chronic kidney disease. Factors that contribute to cancer treatment success include new chemotherapy formulations and schedules that allow higher total dosages, aggressive chemotherapy with stem cell rescue, targeted immunotherapy, novel surgical techniques, and use of multimodality treatment.