Can systemic treatment for lymph node metastasis be given with curative intention? The answer to this question depends on the tumor entity. Therefore we want to give an overview about the role of systemic therapy in the curative treatment of locally advanced urological cancers, such as germ cell tumors, urothelial, renal cell, and prostate cancer. In the case of germ cell tumors cure can be achieved by platinum-based polychemotherapy without any additional treatment modality. This is also true for high-risk germ cell tumors, in which complete remissions and long-term survival are observed following polychemotherapy. In contrast, the role for chemotherapy in locally advanced urothelial cancers so far seems to be confined to (neo-)adjuvant treatment in concert with surgery. Further clinical trials are warranted to standardize and optimize this strategy. So far, renal cell cancer can only be cured by surgery. Cytokines and novel targeted therapies provide a therapeutic option in advanced renal cell cancers. A possible role of the latter modality in adjuvant treatment following resection of high-risk renal cell cancer is currently being tested in randomized trials. The same is true for hormone ablation therapy in locally advanced prostate cancer. In summary, as of today medical therapy can provide cure in advanced germ cell cancers. Its role in all other urological cancers is confined to palliative treatment of non-resectable disease. A possible contribution in the (neo-)adjuvant setting is presently a matter of clinical research.