This COST Action aims to unite researchers with expertise in rational drug design and the medicinal chemistry of synthetic and natural compounds with biomedical investigators dedicated to the understanding the mechanisms governing drug resistance in cancer stem cells. Cancer stem cells (CSC) are a subpopulation of cells within tumors that exhibit enhanced tumor-initiating attributes and are a major contributing factor to current cancer therapy failure. The CSC phenotypic state comprises distinct molecular and functional differences that underpin resistance to current treatments and the unique ability spread and to seed new tumors throughout the body. This insight necessitates an entirely new approach to cancer drug development to effectively target tumor CSCs. Through exchange of information, experience and expertise, researcher mobility and fostering new collaboration between chemistry and biology groups, the Action endeavours to develop new, effective methods for identifying novel compounds and drug candidates that target drug-resistant cancer stem cells.