Within a tumor, Cancer Stem Cells (CSCs) exists and own similar characteristics of a normal stem cell thus contributing towards aggressiveness of cancer by playing crucial role in tumor recurrence and metastasis capability. Various studies have been conducted to therapeutically target CSCs. One of the approaches include is to inhibit cell cycle progression in CSCs. Within last two decades cell cycle and role of various components in its regulation is firmly established. Cell cycle is regulated by Cyclin Dependent Kinases (CDK) bound to cyclin. CDK activity can be blocked by Cyclin-Dependent Kinase Inhibitors (CKIs) which can either bind cyclin/CDK complex or CDK alone and thus stops cell cycle. In this review various studies are discussed that have investigated the therapeutic role of CKIs in eradicating CSCs by inhibiting cell cycle. Overall, the analysis suggests that CKIs could be a potential therapeutic option in controlling CSCs populating in a tumor.