Although radiation therapy has been used as a curative treatment option for patients with localized prostate cancer for decades, there remains a continued need to improve outcomes for patients with localized disease. Systemic therapy in the form of androgen deprivation therapy (ADT) is an important adjunct to radiation therapy which may serve to improve the curative potential of treatment; however, not all forms of systemic therapy which have demonstrated activity in metastatic prostate cancer will improve outcomes for patients with localized disease. Research into the use of radiation therapy with ADT, androgen receptor signaling inhibitors (ARSIs), chemotherapy, poly(ADP-ribose) polymerase (PARP) inhibitors, immunotherapy, and other small molecule inhibitors is ongoing and will help to define not only which of these may be beneficial for patients localized prostate cancer but also which patients may be optimal candidates to receive these adjunctive therapies.