KEY POINTS • The prognosis for patients with mCRPC has improved over the last few years due to the introduction of novel agents. • The optimal sequence of administering these therapeutic agents remains as a moving target and is not well established. Decisions are usually made according to patients' clinical conditions and disease characteristics, and the safety profile and availability of new drugs. • Recently, cabazitaxel improved outcomes in the third-line setting after docetaxel and an ARTA. Olaparib is an additional option for second- and third-line treatment in those with alterations in BRCA1, BRCA2, and ATM. • Understanding the mechanisms of resistance may provide a rationale for suggesting specific strategies. • A subset of patients may benefit from molecularly targeted therapies, which highlights the importance of genomic testing in the castration-resistant setting. • Immunotherapy may provide benefit to some subsets of patients, such as those with MSI-high tumors. Studies regarding combination therapy with immune checkpoint inhibitors are ongoing.