Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer mortality in adult American men, with an estimated 217,730 new cases diagnosed in the U.S. in 2010. Screening for prostate-specific antigen (PSA) has led to earlier detection of prostate cancer. However, elevated serum PSA can be present in other non-malignant conditions, such as benign prostatic hyperplasia and, therefore, PSA screening has a high false positives rate. Active surveillance (AS) of prostate cancer is a current strategy that is used to reduce overtreatment by monitoring of low-risk patients with physical exams, PSA assessments and repeat biopsies, and offering treatment to those with signs of progression. However, nomograms that utilize these predictors of disease progression demonstrate an accuracy of only 61-79% in the clinic. Given the limitations of PSA and significant disease that can be used to categorize patients with localized prostate cancer and assist in treatment decision-making. Several recent studies have shown that serum miRNA signatures have potential value as prognostic tools for prostate cancer.