Tumour heterogeneity is a phenomenon where each cell that makes up a tumour, contains mutations that differ from that of other cells in the tumour. The clonal evolution and cancer stem cell theories of cancer formation, have been used to explain tumour heterogeneity. The theories both point to the existence of cells within a tumour that are capable of initiating the tumour in a different location. While the clonal evolution theory argues that all cells within a tumour possess this ability, the cancer stem cell theory argues that only a few cells (cancer stem cells or CSCs) within the tumour possess this ability to seed the tumour in a different location. Data supporting the cancer stem cell theory is accumulating. Researchers have targeted these CSCs therapeutically, hypothesizing that since these CSCs are the ‘drivers’ of tumour progression, their death may inhibit tumour progression. This was foiled by tumour cell plasticity, a phenomenon whereby a non-CSC spontaneously de-differentiates into a CSC. Researchers are now working on combinations that kill both CSCs and non-CSCs as well as drugs that prevent non-CSC-to-CSC transition. This review concisely describes CSCs and how they contribute to the difficulty in treating cancer.