© 2018 Human Stem Cell Institute. All rights reserved. Cancer stem cells (CSCs) are gaining extensive acknowledge as crucial therapeutic targets for treatment of malignant tumors. CSCs are able to maintain their population and to constantly generate newly differentiated tumor cells. Cancer stem cells that escape treatment are often considered the main source of tumor relapse. Resulting clinical significance had led to extensive studies of stem phenotype-contributing signaling pathways that are often abnormally active in cancer stem cells and CSC-specific traits, that could be used as selective therapeutic targets. Many CSC-targeting therapeutic strategies are currently undergoing clinical trials and evaluation, including various stem cell-specific signaling pathway inhibitors, cancer vaccines based on CSC-primed dendritic cells, monoclonal antibodies and chimeric antigen receptors for adoptive cell immunotherapy.