The metabolism of cancer cells is reprogrammed both by oncogene signaling and by dysregulation of metabolic enzymes. The resulting altered metabolism supports cellular proliferation and survival but leaves cancer cells dependent on a continuous supply of nutrients. Thus, many metabolic enzymes have become targets for new cancer therapies. Recently, two processes—expression of specific isoforms of metabolic enzymes and autophagy—have been shown to be crucial for the adaptation of tumor cells to changes in nutrient availability. An increasing number of approved and experimental therapeutics target these two processes. A better understanding of the molecular basis of cancer-associated metabolic changes may lead to improved cancer therapies.