The notion that microdomains enriched in certain specialized lipids exist i
n membranes has been both attractive and controversial since it was first p
roposed that such domains, termed rafts, might act as apical sorting device
s in epithelial cells. The observation that certain lipids are not extracta
ble in cold nonionic detergent supports the raft concept, but the nature of
the in vivo correlate of such detergent-resistant membranes remains enigma
tic. In principle, microscopy should be able to determine whether the postu
lated rafts exist. This article focuses on recent microscopy experiments ad
dressing this question. Several, but not all, results support the raft conc
ept, but further definition of the structure, dynamics and function of lipi
d domains in various biological contexts is urgently required.