Prostate cancer (PCa) is a common cause of death in men and remains incurable in the androgen-refractory phase. Growing evidence has shown that the androgen receptor (AR) and signal transducers and activators of transcription 3 (STAT3) could be effective targets for androgen-refractory PCa therapy. Many strategies have been reported to inhibit the AR or STAT3 activities. In this review, we focus on the AR N-terminal domain and AR chaperones, as well as small molecule inhibitors to STAT3 with which we discuss some new approaches to target the AR and STAT3 as potential treatments for androgen-refractory PCa.