Post-translational modifiers of the small ubiquitin-like modifier protein (SUMO) family have emerged as key regulators of protein function and localization. SUMO modification is a dynamic process, catalyzed by SUMO-specific E1, E2, and E3 enzymes and reversed by a family of SUMO-specific proteases (SENPs). Although six human SENPs have been identified, each with different cellular locations and substrate specificities, the precise roles of SENPs in cellular processes involved has not been well-defined. This brief review will focus on recent advances about the identified targets of SENP1 and its potential role in tumorigenesis.