Cancer invasion and metastases are the hallmarks of malignant tumors and the cause of most cancer deaths. Molecular alterations that arise during cancer progression and that generate abnormal gene products, activated signal transduction pathways, and altered cancer cell-host stroma interactions can be considered targets of therapeutic drugs. Some of these drugs have already entered clinical trials, while others have shown promising results. In this review, we examine some of the successive steps of the metastatic process: cancer cell migration and invasion of the tumor microenvironment, angiogenesis and following extravasation focusing on the deranged signalling pathways underlying the malignant phenotypes. Finally, the application of new proteomic methodologies to detect cancer earlier and for a patienttailored therapy is illustrated.