There is now compelling evidence for tumour initiating or cancer stem cells (CSCs) in human cancers. The current evidence of this CSC hypothesis, the CSC phenotype and methods of identification, culture and in vitro modelling will be presented, with an emphasis on prostate cancer. Inherent in the CSC hypothesis is their dual role, as a tumour-initiating cell, and as a source of treatment-resistant cells; the mechanisms behind therapeutic resistance will be discussed. Such resistance is a consequence of the unique CSC phenotype, which differs from the differentiated progeny, which make up the bulk of a tumour. It seems that to target the whole tumour, employing traditional therapies to target bulk populations alongside targeted CSC-specific drugs, provides the best hope of lasting treatment or even cure.