Cancer is a major factor of morbidity and mortality worldwide. Over 90% of cancer-related deaths are due to metastatic disease. Observations made more than 140 years ago described cancer cells from solid tumors in the bloodstream. yet, the significance of these circulating and disseminated cells and their contribution to the generation of metastasis remained a mystery. Recently, substantial technological advances have enabled the detection and isolation of circulating tumor cells from the peripheral blood. Currently, this technology allows quantitative analysis of circulating cancer cell content and permits a view of the genetic and phenotypic changes in this accessible population. In the future, researchers hope to use circulating tumor cells as a powerful tool for early detection, prognosis, tumor response assessment and even for treatment selection. The discovery of cancer cells in the bloodstream holds many promises in the study, diagnosis and treatment of cancer, but, at the same time, raises difficult questions regarding the identity of these cells, their contribution to the process of metastasis and their ability to aid medical decisions. This review aims to introduce the topic of circulating tumor cells to the Israeli medical community and encourage active participation in basic and translational research in this field. We believe this field holds great potential for promoting the practice of surgical oncology, tumor surveillance and clinical oncology.