Cancer stem cells (CSCs) are subpopulation of cells within the tumor bulk, which leads to tumor recurrence and therapeutic resistance. Identification of specific CSC targets for detection and efficient cancer therapy are the major hurdles in this research field. In this decade, basic researchers and clinicians made every effort to overcome these challenges to target CSCs using different approaches. This special issue includes a varied collection of review articles with comprehensive discussion on the complexity of CSC heterogeneity, signaling pathways regulating the behaviors of CSCs, the therapeutic resistance mechanism of CSCs, and therapeutic targets against CSCs. These review articles shed light on current advances in understanding of CSC biology.