The metastatic process is an extraordinarily complex step-by-step procedure, characterized by many analogies with migratory patterns of humans or animals across our planet. The ongoing interrogation of circulating tumor cells (CTCs), caught in the act of spreading from one location to another, is revealing distinct behaviors including biological, physical, and mechanical features that impact on their likelihood to form metastasis. In this viewpoint, I will discuss some of these findings and provide a perspective on the metastatic journey, open questions, as well as opportunities to exploit some of the most recent discoveries for the development of anti-metastasis medicines.