Cancer is a major public health problem and the second leading cause of premature deaths worldwide, accounting for an incident rate of 2.6 million cases per year, mainly in Europe and the United States. This book chapter describes the historical aspect of cancer, its treatment modalities and history of natural compounds being used as anti-cancer agents. Role of marine natural compounds and their derivatives in cancer prevention, like, alkaloids, amine derivatives, macrolides, peptides and polypeptides are described in this chapter. Both, role of natural compounds extracted from plants and microbial sources are discussed along with their molecular targets and interactions to kill the cancer cells. Most of the medicinal compounds derived naturally are synthesized semi-synthetically for commercial purposes. They are then formulated into proper dosage increasing their costs. But for many natural compounds clinical trials are still to be carried out to validate their use in cancer therapy.