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Cancer stem cells (CSCs) are a subset of cells within the tumor bulk, with a potential to undergo self-renewal, differentiation, proliferation and metastasis. Cumulative evidences suggest that mainly CSCs are responsible for tumor recurrences and resistance towards chemo- and radiotherapy. Unlike non-stem cancer cells, CSCs can undergo self-renewal and differentiation through asymmetric cell division (ACD) similar to normal stem cells. Asymmetric division results in two daughter cells: a structural and functional copy of the mother cell (CSC) and another one destined to undergo differentiation, non-cancer stem cell. Apart from the involvement of various polarity-determining factors, transcription factors and epigenetic regulators, micro-RNAs also play a crucial role in cell-fate decision making. Eventually, two daughter cells with distinct fates are produced with an unequal inheritance of differentiation-linked fate determinants, centrosomes and other stemness associated factors. Violation of the mechanisms leading to ACD will compromise the generation of both new CSCs and progenitor cells within the tumor. Thus, manipulation of asymmetric division of CSCs may introduce new strategies for dual targeting of CSCs and the tumor bulk. In this review, we discuss how CSCs play a critical role in almost all the events of tumorigenesis. Apart from that, we also delineate how these CSCs exploit the phenomenon of ACD during cancer relapses or tumor recurrences to regenerate the entire tumor. Therefore, in a nutshell this review highlights the therapeutic relevance of CSCs for successful elimination of cancer and suggests a novel improvisation in CSC-targeting by perturbing its ACD mechanisms.