Patients with high-risk, localized prostate cancer have an increased risk of developing metastases and experiencing prostate cancer-specific death compared to those with low- and intermediate-risk disease. The results of the STAMPEDE trial changed the standard of care for these patients, improving survival endpoints by intensifying androgen deprivation therapy (ADT) with the addition of abiraterone. Given the STAMPEDE data and the benefit of other second-generation androgen receptor inhibitors (ARIs) in later lines of therapy, researchers are evaluating the impact of utilizing ARIs earlier in the continuum of prostate cancer care. Despite growing consensus among experts that ADT alone is not enough for most high-risk patients with localized disease, treatment intensification remains underutilized. Our goal is to educate oncologists, urologists, radiologists, and other treatment team members on the duration of treatment, safety, and efficacy profiles of approved treatments as well as to provide additional insights on their potential for application in earlier settings.