There is now compelling evidence for tumour initiating or cancer stem cells (CSCs) in human cancers. Inherent in the CSC hypothesis is their dual role, as a tumour-initiating cell, and as a source of treatment-resistance. It seems that, employing traditional therapies targeted towards bulk populations alongside targeted CSC-specific drugs will provide best therapeutic benefits. However, the mechanisms behind therapeutic resistance in CSC are still not known. Our laboratory is actively pursuing how cancer stem cells escape the therapy induced apoptosis and also exploring their role in cancer progression. Expression profiles of stem cells from normal and resistance models that we have generated in our lab are being used as a platform to directly examining the candidate pathways regulating resistance and propagation in cancer stem cells.