Rel/NF-κB transcription factors are key regulators of genes implicated in inflammatory and immune activation, cell growth and protection from apoptosis. Constitutive activation of NF-κB has been observed in several types of cancers. Recently, it has been shown that inflammation and cancer are molecularly linked by means of NF-κB. During prostate cancer progression, NF-κB promotes cell survival, tumor invasion, metastasis and chemoresistance. NF-κB constitutive activation has been frequently demonstrated in primary prostate cancers and it correlates with loss of androgen receptor expression and castration-resistant phenotypes. Indeed, inhibition of NF-κB pathway may reduce the oncogenic effects mediated by chronic inflammatory response. Therefore, NF-κB represents a hopeful target for the treatment of prostate cancer due to its role in oncogenesis and chemoresistance. Here, the current knowledge about the roles of NF-κB signaling pathway in prostate tumorigenesis is discussed, taking into consideration the potentiality and effectiveness of NF-κB inhibitors as therapeutic agents for prostate cancer.