Lipid rafts and caveolae are microdomains of the plasma membrane enriched in sphingolipids and cholesterol, and hence are less fluid than the remainder of the membrane. Caveolae have an invaginated structure, while lipid rafts are flat regions of the membrane. The two types of microdomains have different protein compositions (growth factor receptors and their downstream molecules) suggesting that lipid rafts and caveolae have a role in the regulation of signaling by these receptors. The purpose of this review is to discuss this model, and the implications that it might have regarding a potential role for lipid rafts and caveolae in human cancer. Particular attention will be paid to the epidermal growth factor receptor, for which the largest amount of information is available. It has been proposed that caveolins act as tumor suppressors. The role of lipid rafts is less clear, but they seem to be capable of acting as 'signaling platforms', in which signal initiation and propagation can occur efficiently.