OBJECTIVE To evaluate the efficacy of non-steroidal anti-androgen monotherapy in the treatment of advanced prostate cancer. METHODS The pertinent literature regarding the use of nilutamide, flutamide, and bicalutamide as monotherapy in the treatment of prostate cancer has been reviewed. RESULTS The clinical utility of non-steroidal antiandrogen monotherapy is currently under investigation. As with other endocrine therapies, this approach appears to provide effective palliation of symptoms, but offers certain quality-of-life benefits, including preservation of libido and sexual potency, issues which may be important in certain patients, particularly younger men. Available data indicate that flutamide may be as effective as orchidectomy in terms of prolonging progression-free survival in selected patients. Nilutamide has been less extensively investigated, but the clinical utility of this agent, except for use in combined therapy, would appear to be somewhat limited by a high incidence of drug-related side effects. Bicalutamide, however, is well tolerated as monotherapy and appears to be as effective as castration in patients with locally advanced non-metastatic disease. In metastatic disease, the improved subjective response and quality of life gains with bicalutamide may outweigh the slightly inferior survival. CONCLUSIONS These promising preliminary findings, a number of issues remain to be determined before non-steroidal antiandrogen monotherapy can be considered to be routine clinical practice. These include optimum indication and dosage, long-term clinical efficacy and tolerability, and response to second-line therapy.