High mobility group box 1 (HMGB1) is a non-histone protein required to maintain chromatin architecture. Recent observations demonstrated that HMGB1 can also act as a cytokine to regulate different biological processes such as inflammation, cell migration and metastasis. We showed previously that HMGB1 can be released passively by cells that die in a traumatic and unprogrammed way, and can serve a signal of tissue damage. More recently, we showed that HMGB1 can recruit stem cells: HMGB1 induces stem cell transmigration through an endothelial barrier; moreover, when beads containing HMGB1 are implanted into healthy muscle, they recruit stem cells injected into the general circulation. The inflammatory and tissue-regenerating roles of HMGB1 may be strictly interconnected, and are discussed here.