There has been considerable recent interest in the possibility that the plasma membrane contains lipid "rafts," microdomains enriched in cholesterol and sphingolipids. It has been suggested that such rafts could play an important role in many cellular processes including signal transduction, membrane trafficking, cytoskeletal organization, and pathogen entry. However, rafts have proven difficult to visualize in living cells. Most of the evidence for their existence and function relies on indirect methods such as detergent extraction, and a number of recent studies have revealed possible problems with these methods. Direct studies of the distribution of raft components in living cells have not yet reached a consensus on the size or even the presence of these microdomains, and hence it seems that a definitive proof of raft existence has yet to be obtained.