Abstract Cancer stem cells (CSCs), a unique subset of undifferentiated cells with stem cell-like properties, have emerged as driving forces in mediating tumor growth, metastasis, and therapeutic resistance. Recent advances have highlighted that N6-methyladenosine (m6A) RNA modification plays an important role in cancer biology and CSCs. Dynamic m6A decoration has been demonstrated to be involved in CSC generation and maintenance, governing cancer progression and therapeutic resistance. In this review, we provide the first overview of the current knowledge of m6A modification implicated in CSCs and their impact on CSC properties, tumor progression, and responses to treatment. We also highlight the potential of m6A machinery as novel targets for cancer therapeutics. The involvement of m6A modification in CSCs provides a new direction for exploring cancer pathogenesis and inspires the development of effective strategies to fully eliminate both cancer cells and CSCs.