Use of immunotherapy in recent years has revolutionized cancer treatment for certain types of cancers. However, the broad utility of immunotherapy is limited because there are still many types of cancer that do not respond effectively. Failure of a cancer to respond is due, at least in part, to its phenotypic plasticity, a feature that is established by cancer stem cells (CSC) and their associated microenvironments. This article discusses the current understanding of CSC-mediated immune evasion and provides a prospective view on how researchers can better understand and overcome the intrinsic immune privilege of CSCs and the extrinsic immune-suppressive microenvironment shaped by them.