Open AccessMost cancer-related deaths are due to the development of metastatic disease rather than the growth of primary tumors. Adjuvant treatment often does not translate into substantial improvements in overall survival; subclinical micro-metastases may be resistant to multiple therapies. Understanding microenvironment factors such as hypoxia, proliferation and glucose metabolism in micro-metastases is of importance for micro-metastases treatment; hypoxia, commonly observed in most primary solid malignancies, is associated with tumor progression, increased aggressiveness, enhanced metastatic potential and poor prognosis and hypoxic tumor cells are more resistant to radiotherapy and some forms of chemotherapy. In this article, we discussed hypoxia status of micro-metastases, and related this to cellular proliferation and glucose metabolism. We also proposed hypoxia as a therapeutic target for micro-metastases.