Second only to skin cancer, cancer of the prostate gland (CaP) is the most commonly occurring cancer in American men. Existing treatment approaches and surgical intervention have been unable to effectively manage this dreaded cancer; therefore, efforts are ongoing to explore novel targets and strategies for the management of CaP. A complete understanding of the genetic control of the processes of cellular proliferation and programmed cell death, or "apoptosis," may provide the basis for the rational design of novel therapeutic strategies against CaP. Key regulators for the mitotic progression in mammalian cells are the polo-like kinases (Plks). The activity of Plk1 is elevated in tissues and cells with a high mitotic index, including cancer cells. An increasing body of evidence suggests that the level of Plk1 expression has prognostic value for predicting outcomes in patients with some cancers such as lung cancer, squamous cell carcinomas of the head and neck, melanomas, and ovarian and endometrial carcinomas. However, the role of Plk1 in CaP is not known. Here, a hypothesis is put forward that Plk 1 plays a critical role in the development of prostate cancer; and the silencing of Plk1 will result in elimination of human CaP cells via an inactivation of cyclin-dependent kinase 1 (Cdc2)/cyclin B 1-mediated mitotic arrest followed by apoptosis. A corollary to this hypothesis is that Plk1 could serve as a target for the intervention of CaP in humans. Therefore, if the hypothesis is tested to be true, it is conceivable that gene therapeutic approaches aimed at Plk1 or the pharmacological inhibitors of Plk1 may be developed for the treatment/management of CaP.