Prostate cancer (PCa) is the second most common cancer in men. Androgen receptor (AR) signaling pathway plays a crucial role in prostate development and homeostasis. Dysregulation of this pathway activates AR leading to PCa pathogenesis and progression. AR binds testosterone and other male hormones, which then undergoes post-translational modification for AR nuclear translocation and transcriptional activation. AR activation by post-translational modification is thus imperative for PCa cell growth and survival. Identification and understanding of the pathological and mechanistic roles of AR modifications may increase our understanding of AR activation in PCa and provide new therapeutic options. Recently, AR acetylation has been described as an important step for AR activation. Upregulation of several acetyltransferases has been reported to be associated with PCa progression. Herein, we provide a general understanding of AR acetylation, with a special emphasis on ARD1, and potential therapies that may be exploited against the ARD1-AR axis for PCa treatment.