Kidney cancer, although relatively rare when compared to other malignancies, occurs not uncommonly in patients with renal disease and is often discovered incidentally during the initial nephrologic work-up, or by the savvy clinician who is familiar with the paraneoplastic signs. While surgical approaches are generally curative when the disease is confined to the kidney, one-third of the cases that present in the metastatic form and require conventional medical therapy are associated with a truly dismal patient survival rate. In light of the emerging knowledge of the molecular mechanisms of kidney cancer oncogenesis, several novel and promising therapeutic approaches are emerging. In this review, we summarize the current state of kidney cancer diagnosis and therapy, as well as some of the novel treatments that capitalize on those newly elucidated molecular pathways that are deranged in this disease.