Prostate cancer (PC), the second most prevalent malignancy in men worldwide, has been proven to depend on the aberrant activation of androgen receptor (AR) signaling. Longterm androgen deprivation for the treatment of PC inevitably leads to castration-resistant prostate cancer (CRPC) in which AR remains a crucial oncogenic driver. Thus, there is an urgent need to develop new strategies to address this unmet medical need. Targeting AR for degradation has recently been in a vigorous development stage, and accumulating clinical studies have highlighted the benefits of AR degraders in CRPC patients. Herein, we provide a comprehensive summary of small-molecule AR degraders with diverse mechanisms of action including proteolysis-targeting chimeras (PROTACs), selective AR degraders (SARDs), hydrophobic tags (HyT), and other AR degraders with distinct mechanisms. Accordingly, their structure− activity relationships, biomedical applications, and therapeutic values are also dissected to provide insights into the future development of promising AR degradation-based therapeutics for CRPC.

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