Every year about 7 million people die from of various types of cancer, making this disease responsible for 12.5% of deaths worldwide. Consequently, there is an overwhelming demand to develop new, more potent and effective, anticancer drugs. Natural products represent the most valuable source with inexhaustible reserves, in which the researchers work could identify novel active agents that may serve as the leads and scaffolds for transformation into desperately needed efficacious drugs. This paper is devoted to reviewing some of the most outstanding achievements in the application of natural products as models and precursors for anticancer agents published in the post 2000 literature. Particular emphasis is placed on the chemical modification of active principles isolated from natural products, in hope of obtaining the desirable derivatives for the treatment of different types of cancer, including pancreatic, gastric, breast, colon cancers and leukemia.