Polo-box domain 1 (PBD1) is a characteristic domain of polo-like kinase 1 (PLK1), which locates in C-terminal and can influence the catalytic activity and specific subcellular locations of PLK1.  At present, most PLK1 inhibitors are developed to occupy the ATP pocket or its close sites.  However, this kind of PLK1 inhibitors is difficult to pursue target selectivity and may encounter cross drug resistance with other kinase inhibitors due to the conserved sequence of ATP pocket.  Recently, PBD1, with aberrant specificity in sequence and structure, has attracted enormous interests as the alternative target to the discovery of corresponding inhibitors for anti-tumor drugs.  The structure and function of PBD1 as well as the advances of its inhibitors are reviewed in this paper.