Recurrence rates of approximately 35-65% after nephrectomy in patients with localized or locally advanced renal cell carcinoma clearly underline the need for adjuvant treatment modalities. Adjuvant treatment with cytokines, hormonal treatment and radiotherapy has not shown survival benefit. The only Phase III trial revealing significant prolongation of progression-free survival was published in 2004. In this trial, targeting the immune system using an autologous tumor-cell vaccine provided clinical efficacy, but as yet, no standard adjuvant therapeutic approach is available. Recent advances in understanding the molecular biology of renal cell carcinoma led to the development of several targeted agents showing antitumor efficacy and prolongation of progression-free survival in patients with metastatic kidney cancer, but to date, no data are available regarding their applicability and efficacy in the adjuvant setting. However, controlled trials applying these drugs in the adjuvant setting have already started and, hence, the question is raised as to whether there is still a role for vaccination immunotherapy in the era of targeted therapies. In this paper, results from current Phase III trials and other relevant studies regarding adjuvant treatment in renal cell carcinoma are reviewed with special interest on adjuvant vaccination therapies, particularly regarding future options of this therapeutic approach.