Cancer metastasis accounts for over 90% of cancer death.However, its mechanisms are still poorly understood and the current approaches to prevent or treat human metastatic diseases are mostly unsuccessful.Through genomics, RNAi and cDNA functional screens using cell culture and mouse models, we have identified a number of human genes that may play important but previously unknown roles in cancer metastasis.Two groups of genes are currently under active investigation for their signaling pathways and molecular mechanisms: (1) essential kinases that are indispensible for survival and proliferation of metastatic cells, one of these kinases is also sufficient to promote primary tumor growth and metastasis when ectopically expressed in non-metastatic cells.