Cancer is the world’s second leading cause of death after heart diseases, and involves abnormal cell growth at a primary site and the potential to spread to other parts of the body. Tumors are highly heterogeneous and consist of subgroups of cells with distinct characteristics. Of these, the cancer stem cells (CSC) niche plays a crucial role in driving the spread of the tumor and are thought to provide treatment resistance. CSC is a rare special population of cancer cells exhibiting high tumorigenic properties together with self-renewal and differentiation capability. CSC is not only linked with high tumor-initiating activity, but is also implicated in chemotherapeutic re-sistance, metastasis, epithelial to mesenchymal transition, and recurrence. Thereafter, novel ther-apeutic strategies targeting CSC are in need in order to improve long-term clinical outcome. The literature supports the evidence that marine natural compounds can exhibit antioxidant, antimitot-ic, anti-inflammatory, anti-biotic as well as anticancer activity. In this review, we will provide an insight into the relevance of selected marine natural products as a source of bioactive compounds with anti-cancer properties, and to target CSC, which may benefit the development of novel anti-cancer therapeutic strategies.