Antiandrogen therapy (AAT) is a common adjunct treatment for prostate cancer (PCa) patients and has shown significant benefits to long-term outcomes from radiation or surgery. Although AAT has some adverse side effects and data from breast cancer patients indicate that such side effects from hormonal therapies may contribute to anxiety and depression and may also hinder AAT treatment compliance, this issue has not been investigated within a sample of PCa patients. This study explores the incidence of AAT side effects in a sample of PCa patients, the links between those side effects and anxiety and depression, the possible ways in which these factors may contribute to AAT treatment noncompliance in PCa patients, and how psychosocial treatments might be developed to attend to this issue. 147 PCa patients completed questionnaires on demographic factors, treatment compliance, AAT side effects, anxiety and depression. About 18% of the sample reported AAT side effects, and there was a significant association between the presence of side effects and elevated anxiety and depression scores. Increased frequency of side effects was significantly associated with elevated anxiety, but not depression. The most powerful relationship between AAT side effects and anxiety-depression was for the subfactors of (1) Fatigue, Pain and Discomfort, and (2) Psychological Agitation and Pessimism. Although fatigue, pain, and discomfort may be outcomes of the hormonal treatment itself, psychological agitation and pessimism represent a discrete psychological pathway between AAT side effects and anxiety and depression and (potentially) treatment noncompliance. Methods of addressing patients' loss of optimism in their treatment outcomes are discussed.