Stem cells are vital for regenerating and repairing the organs such as the heart, lungs, skin, germ cells and other tissues. But the characteristics of normal stem cells and the discovery of origin of leukemia have headed the scientist to the hypothesis that cancer may initiate from stem cell-like cells. Cancer stem cells are now thought to be responsible for cancer initiation, progression, metastasis, recurrence and drug resistance. There are some similarities and differences between CSCs and healthy stem cells in signaling pathways (Wnt/β–catenin, Hh, Notch), epigenetic modifications, telomere maintenance, and degree of dependence on the stem cell niche, maintenance of multipotency and self-renewability of respective progenitor cells. Distinct and specific surface biomarker phenotypes can be used to distinguish CSC from other tumor cells and normal stem cells through single and combination of markers such as CD44, CD34+ CD38 −and CD133. Recently, miRNAs have been tried as a marker and therapeutic agents against cancers stem cell such as miR-34a, miR-199a, miR-181, miR-125b-2 and miR-128. However, targeting CSCs without harming their normal counterparts is an advantageous way in the design of novel therapies but many questions remain unknown.