Despite present-day clinical achievements which can extend the overall survival period, prostate cancer (PCa) related mortality remains a major problem. Resistance against apoptosis which consequently leads to disease prognosis is one of the most important characteristics of metastatic cancer cells which display a high level of genetic and clinical heterogeneity. Therefore, achievements in the local treatment of PCa have not been matched in the treatment of the metastatic disease. Although androgen deprivation therapy is the standard treatment due to the androgen receptor (AR) signaling pathway which has primary importance in metastatic cases, successful treatment remains difficult because of the genetic aberrations of ARs. Majority of the PCa patients develop resistance against androgen ablation within an average of 12-36 month-period and despite the castrate levels of testosterone, androgen-dependent and independent signals cause an increase in the cancer cells. While effective survival advantages displayed by the new generation agents like abiraterone and enzalutamide is promising in the treatment of metastatic castration resistant PCa how to best manage the primary and secondary resistance to treatment remains a challenge. The apoptotic effect enhancing pro-survival effectors and apoptotic regulators within the cytoprotective chaperone networks become more and more important every day for overcoming treatment resistance. Recent scientific research on apoptotic pathway inducing mechanisms focuses on the importance of developing synergistic treatment strategies. Molecules with lower side-effect profiles which are capable of inducing physiological mechanisms like apoptosis are expected to replace chemotherapeutic agents in the future.