The Cdc25 phosphatases function as key regulators of the cell cycle during normal eukaryotic cell division and as mediators of the checkpoint response in cells with DNA damage. The role of Cdc25s in cancer has become increasingly evident in recent years. More than 20 studies of patient samples from diverse cancers show significant overexpression of Cdc25 with frequent correlation to clinical outcome. Recent screening and design efforts have yielded novel classes of inhibitors that show specificity for the Cdc25s over other phosphatases and cause cell cycle arrest in vivo. Herein we provide a single source for those interested in the cellular functions of Cdc25 in cell cycle progression, its role in the progress of cancer and survival of cancer patients, and recent efforts in the design of specific inhibitors.