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Simple Summary: Following local treatment of prostate cancer by surgical removal or radiation, biochemical recurrence may occur and progress to castration resistance (CR) following androgen deprivation therapy (ADT). If disease persists, men develop metastatic disease (mCRPC) which leads to death. Prior to mCRPC, a non-metastatic state exists (nmCRPC) characterized by a rise in PSA and lack of detectable metastases. Here, we review potential therapeutic strategies to interfere with the transition before the cancer becomes deadly. Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay; however, some patients will transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC may develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, however, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC. [ABSTRACT FROM AUTHOR]