Tumour heterogeneity has several important consequences including: (i) making their classification by morphological and genetic analysis more difficult because of the diversity within single tumours and the common majority of cells as the bulk of a tumour will dominate this classification whether or not these cells are critical for diagnosis or treatment, (ii) treatments may fail to eradicate tumours simply by failing to eliminate one of the cell subtypes within the tumour and (iii) differing abilities of the cell subtypes for dissemination and metastasis. Recently, a rare subpopulation of cells within tumours has been described with the ability to initiate and sustain tumour growth, to resist traditional therapies and to allow for secondary tumour dissemination. These cells are termed tumour-initiating cells (TICs). Understanding tumour heterogeneity will be critical for advancing treatments for cancer that target TIC subpopulations of cells in a tumour able to resist traditional treatments and eliminate them before metastatic disease occurs. It follows that the TICs will be the most important cellular components in the tumour target. Therefore, knowledge of the molecular mechanism(s) of resistance of TICs to treatment and overcoming this problem will be essential in order to develop effective drug strategies for cancer therapy.