Epithelial-mesenchymal transition (EMT) is a dynamic process by which the cells transdifferentiate into two or more somatic states. The metastatic spread begins with tumor cells disseminated from the primary tumor via intravasation, hematogenous transit and extravasation to reach the distant organs to form micro- or macrometastasis. Dissemination of tumor cells or metastasis is a crucial stage in cancer progression and accounts for majority of cancer associated morbidity and mortality. Advances in technology has now enabled detection and capture of tumor cells that escape from primary site into the bloodstream. Such tumor cells which are found in transit in the blood are referred to as circulating tumor cells (CTCs) and they represent the early step in metastatic cascade. The dynamic changes in EMT phenotype in CTCs plays a key role in cancer metastasis. This review will focus on the role of EMT in cancer progression, circulating tumor cells and its clinical relevance.