Despite the fact that cancer is a leading cause of death world wide, a clear understanding of the causes, processes, and epidemiology of cancer remains elusive. Nevertheless key players are being identified, such as cancer stem cells, a subset of cells that are capable of self-renewal and generation of a variety of cells that comprise the tumor. Cancer stem cells also constitute a motor for disease maintenance, being able to resist radio and chemotherapy leading to disease recurrence. This paper provides an overview of stem cell biology, covering the mechanisms of how abnormal cancer stem cells emerge. The search for relevant therapeutic targets has been driven by the fact that cancer stem cells resist common anti-cancer strategies. Thus, this review focuses on the current strategies under development to target cancer stem cells. These approaches tackle various fronts of disease progression: at the sub-cellular level, by interfering with telomerase activity, protein synthesis and membrane receptor activation, at the tissue/organ level by affecting angiogenesis, and at the organism level, through vaccines stimulating the immune system against cancer stem cells. Herein, I review various patents and upcoming technologies to develop therapies targeting cancer stem cells.