Maspin is a unique serpin with diverse biological functions. Initially identified from human normal mammary epithelial cells, maspin expression is either reduced or completely silenced in breast cancers. Numerous studies have implicated maspin function in cancer progression and angiogenesis. Maspin has also been targeted for breast cancer gene therapy. Recently, transgenic and gene knockout mouse models have been used by our laboratory to identify the biological functions of maspin in vivo. In this review, we summarize the multiple functions of maspin in tumor progression and mouse development. These data demonstrate that maspin not only plays a role in tumor progression and metastasis but also is a key regulatory molecule for normal mammary gland and embryonic development.