As prognosis following a cancer diagnosis has improved and survival has increased, so has the occurrence of multiple primary cancers diagnosed in the same individual. In the United States, one in five cancer diagnoses involves an individual with a previous history of cancer. These new primary cancer diagnoses, or “subsequent neoplasms” (SN), are a substantial cause of morbidity and mortality in cancer survivors. The risk of developing SN varies substantially depending on age, the type of initial primary cancer, chemotherapy, radiotherapy, genetic susceptibility, and exposure to other cancer risk factors. Childhood cancer survivors have particularly elevated SN risks associated with radiotherapy and, to a lesser extent, systemic therapy. Genetic susceptibility to cancer is also thought to play an important role in SN development after childhood cancer. Survivors of many adulthood cancers also have elevated SN risks, likely with a multifactorial etiology.