Evidence has accumulated over the past few years to suggest that specialized plasma membrane regions enriched in cholesterol and glycolipids, called 'lipid rafts', are primarily involved in the initiation and propagation of the signal transduction cascade associated with lymphocyte activation. Considering the multitude of recent and often contradictory data, however, it appears that a critical reconsideration of the role of lipid rafts in lymphocyte activation is necessary and timely, particularly in light of a series of new experimental results that challenge the traditional view of the role of lipid rafts in lymphocyte activation.