Metastasis suppressor proteins regulate multiple steps in the metastatic cascade, including cancer cell invasion, survival in the vascular and lymphatic circulation, and colonization of distant organ sites. Understanding the biology of metastasis suppressors provides valuable mechanistic insights that may translate to therapeutic opportunities. Several reports have explored novel strategies for restoring metastasis suppressor function, including gene transfer, induction of previously suppressed gene expression and exogenous administration of gene product. Pathways activated downstream of metastasis suppressor loss can also be targeted. Although none of these strategies are yet in routine clinical use, several are being tested preclinically and in clinical trials.