Renal cell carcinoma (RCC) is a heterogenous group of cancers that arise from the nephron. While there are distinct histologic subtypes associated with common genetic alterations, most forms of RCC are linked by a common pathway of dysregulated metabolism. Reliance on aerobic glycolysis, a feature of cancer first hypothesized by Warburg, is a common feature in sporadic and hereditary forms of kidney cancer. Two hereditary forms of RCC, succinate dehydrogenase (SDH) and hereditary leiomyomatosis and RCC (HLRCC), are characterized by mutations in Krebs cycle enzymes, rendering them dependent on glycolysis for energy requirements. The reliance on these pathways may make them vulnerable to novel metabolic strategies, including inhibition of glycolysis, glucose uptake and macromolecule biosynthesis.