Limited treatment options exist for metastatic castrate-resistant prostate cancer (mCRPC). The concept of targeting tumors via anti-angiogenic mechanisms has been studied over the last decade, giving rise to a new class of anti-cancer drugs. Currently, the use of angiogenesis inhibition in prostate cancer is the focus of many ongoing clinical trials, with tumor progression and overall survival established as outcome measures. Several anti-angiogenic agents are currently under investigation with varying mechanisms by which they exert activity against prostate tumors. We describe the significant findings and outcomes of clinical trials involving the use of these drugs in mCRPC patients, along with how these results will translate to their use in the clinical setting. Open interventional trials that are currently recruiting participants are also mentioned. While the use of angiogenesis inhibition holds promise in the treatment of prostate cancer, several challenges still exist. The foreseeable clinical implications and limitations of anti-angiogenic therapy and the potential use of biomarkers are hereby discussed.