ABSTRACT Cell membranes are fluid but can exhibit local order that gives rise to lateral inhomogeneities, often referred to as membrane microdomains. Among the best studied yet least well understood of these microdomains are lipid rafts. Lipid rafts are hypothesized to participate in a variety of physiologic and pathologic pathways important to human health by causing the spatial segregation of proteins and lipids within the plane of the membrane. Despite the widespread implications of the raft model, major questions remain about raft size, composition, and life span. This article discusses how recent biophysical measurements of the dynamic properties of rafts and putative raft-associated proteins and lipids are being used to test the hypothesis that confinement of proteins in rafts slows and/or impairs their ability to sample their microenvironment by lateral diffusion.