The lung offers circulating tumor cells—after their initial development as primary tumors and their selection for metastasis to other organs of patients—several optimal conditions for survival and progression that may be unique to this organ. First, the lung is highly oxygenated and provides maximal oxygen tension required for the aggressive metabolism that occurs in most tumor cell populations. Second, the lung offers a vast array of small blood vessels that are required for oxygen: CO2 exchange and for nutrient:catabolite exchange; this microvasculature serves the very active metabolic requirements of tumor cells very effectively. Third, the lung is the first or second organ encountered by tumor cells when they are “liberated” from primary tumors. Fourth, the endothelial/intimal linings of the small blood vessels of the lung may offer adhesion and/or migration sites for tumor cells that are more facile than blood vessels in many other organs. In these regards, a contrast is provided by micrometastases that develop in the lung vs those in bone where oxygen/nutrient/blood vessel availabilities are much more limited. For these and many other reasons, metastasis to the lung may be a more efficient process than metastasis to other organs.