Major current cancer strategies like surgery, radiotherapy, and chemotherapy are compromised due to major problem of recurrence, which usually lead to mortality. The widely accepted reason for this is resistance offered by cancer cells towards cancer drugs or inability of a therapeutic procedure to target real culprits viz. cancer-initiating cells (cancer stem cells). So, there is a current need of development of new agents targeting these cancer stem cells in order to overcome resistance to therapeutic procedures. The present review article is focused on new cancer cell targeting agents like salinomycin, apopotin etc and their mechanisms to target cancer stems cells will be discussed.