Current models of primary cancers suggest that tumour formation and growth is due to a rare subpopulation of stem cell-like tumour-initiating cells. These cells have the capability of self-renewal and the ability to form all cell types of the heterogenous tumour. Due to the nature of the metastatic process, where only a small number of primary cells are capable of successfully forming a metastasis, it is suggestive that metastases may also form from a rare tumour-initiating population. Currently, the existence and origin of these putative metastasis-initiating cells is unclear. Here we aim to discuss current evidence for such a metastasis-initiating cell population, and the potential models for the origin of these cells. The therapeutic implications of targeting chemo- and radioresistent primary tumour-initiating cells may also apply to the treatment of metastatic disease.