Androgen deprivation therapy for prostate cancer is associated with several complications, including loss of libido, hot flashes, night sweats, psychological stress, osteoporosis, anemia, fatigue, loss of muscle mass, glucose intolerance, and changes in lipid profile. The natural history of prostate cancer while on such therapy is the attainment of an incurable androgen-independent state. Early diagnosis by prostate-specific antigen screening, longer life expectancies, and a penchant for immediate therapy pose a problem where clinicians have to balance the potential benefits of early hormonal therapy with the risks of development of these metabolic and psychological complications. Intermittent androgen deprivation offers clinicians a prospect to improve quality of life in patients with prostate cancer by harmonizing the benefits of androgen ablation with a reduction in treatment-related side effects and expenditure. In this review we discuss the challenges and opportunities of this mode of therapy and shed light on some of the underlying molecular mechanisms.