Cancer stem cells (CSCs) are a small subpopulation of cells within a tumor that have properties similar to normal stem cells. That means they are capable of self-renewal and can generate different types of cells found in a specific cancer. This makes them highly tumorigenic, meaning they are a key driver of tumor growth, and they are believed to be responsible for cancer initiation, recurrence, and metastasis. In this special issue we will present novel findings on cancer stem cells with special emphasis on innovative therapies, especially repurposing existing drugs and using phytonutrients for targeting cancer stem cells.