Abstract The majority of human tumours are comprised of cancerous epithelial cells that coexist with a multitude of different cell types and extracellular matrix components creating the cancer microenvironment. Cancer-associated fibroblasts (CAFs) are the most abundant mesenchymal cell types present within most human carcinomas. Recent evidence suggests that nutrient deprived epithelial cancer cells are able to survive these conditions, as a result of their ability to undergo extensive metabolic reprogramming and exploit the metabolic capacities of surrounding CAFs. Although several studies support the role of CAFs in tumour progression and metastasis, the molecular mechanisms underlying this pro-tumourigenic interaction remains to be elucidated. This review will discuss the complex metabolic interaction that exists between epithelial cancer cells and CAF’s: focussing primarily on their functional role in tumour progression, metastasis and chemotherapeutic resistance. Attempts are made at delineating the molecular mechanisms underlying this pro-tumourigenic interaction, and potential CAF-based targets are suggested.