Prostate cancer initially responds to therapies that reduce testosterone level but resistance develops thereafter. Progression of disease despite castrate levels of testosterone was termed as "hormone refractory" or "androgen-independent" initially. However preclinical studies showed that prostate cancer cell develops many mechanisms to survive in androgen-poor environment such as; androgen receptor mutations and intratumoral steroidogenesis. Those adaptive mechanisms retain the prostate cancer cell castration resistant but still hormone sensitive. In castration resistant prostate cancer, two new hormonal treatment molecules were shown to improve survival and approved by FDA in last two years. Enzalutamide and abiraterone acetate will be reviewed in this chapter.