Prostate is cancer is the most commonly diagnosed cancer in men worldwide and the second biggest killer among cancer related deaths in men. Due to advances in both detection as well as treatment, the disease can often be caught early when it is still confined within the prostate gland. The prognosis of patients when the disease is still confined within the organ is generally good. However, the prognosis in patients when the disease has spread to regional lymph nodes is very poor. Metastatic prostate cancer accounts for nearly all the mortality associated with prostate cancer. Numerous clinical studies have documented the importance of lymph node involvement in predicting patient survival. These data suggest that not only is lymph node involvement an important indicator of systemic metastases, they may be an active participant in the process. In the present report, we provide insight into mechanisms that are involved in prostate cancer metastasis to lymph nodes. First, we examine the relationship between the lymphangiogenic mechanisms and prostate dissemination to lymph nodes. Second we, offer insight into lymph node specific homing mechanisms used by prostate cancer cells. Finally, we describe a strategy to interrogate the significance of lymph nodes as a reservoir of malignant cells that can fuel future metastatic dissemination. A better understanding of the mechanisms involved in lymph node metastasis will allow us to better treat the metastatic disease.