Cancer, which accounted for 7.9 million deaths (around 13% of all deaths) in 2007, is a leading cause of death in the world. Deaths from cancer worldwide are projected to continue rising, with an estimated 12 million deaths in 2030. Therefore, the rapid increase in the cancer burden represents a real crisis for public health and health systems worldwide. Although cancer chemotherapy will cause side effects and drug resistance, it is still recognized as the first choice for the treatment of many cancers. To our knowledge, naphthalimide (1H-benzo[de]isoquinoline-1,3-(2H)-dione) analogs have been considered as one promising and potential class of anticancer agents against human tumor cells, such as amonafide (Quinamed(R)) was the first naphthalimide analog that reached the clinical trial stage and exhibited excellent antitumour activity against advanced breast cancer. In this review, we make attempts to report recent advances on the synthesis of naphthalimide analogs, including mononaphthalimides, bisnaphthalimides, and naphthalimide-other heterocycles conjugates; in the meantime, the relationships between the structures of the naphthalimides and the antitumour activity are investigated in detail. It will pave the way for the design and development of naphthalimide analogs as anticancer agents.