Metastasis, or tumor growth in an ectopic site, may occur several years after apparently successful treatment of the primary malignancy. Clinical dormancy is seen in a large number of cancer patients, but once growth in an ectopic site initiates, current adjuvant therapies are inadequate and the majority of patients with metastatic disease will die. Many genes may regulate ectopic growth in a secondary site, including a small subset, termed the metastasis suppressor genes. Investigation into this class of genes holds promise in terms of gaining a greater understanding of tumor dormancy and how the process of metastasis may be naturally inhibited. This review will focus on the role of metastasis suppressor genes in tumor dormancy. Insights into the metastatic process from studies of metastasis suppressor genes may lead to novel targets for antimetastatic therapy through drug-induced reactivation of one or more of these genes and/or their respective signaling pathways.