1. Introduction 373
2. Are rafts probable? 374
3. Micro-, nano- or ephemeral domains? 375
4. How can we reliably assess ‘raft’ composition? 376
5. Are rafts plausible? 379
6. What more can model systems contribute to ‘raft’ studies? 381
7. References 382
The concept of ‘lipid rafts’ and related liquid-ordered membrane microdomains has attracted great attention in the field of membrane biology, both as a novel paradigm in models of membrane organization and for the potential importance of such domains in phenomena such as membrane signaling and the differential trafficking of various membrane components. Studies of biological and of model membranes have gone hand in hand in shaping our current picture of the possible organization and functions of liquid-ordered lipid microdomains in membranes. This essay discusses some important current questions concerning the existence and functional importance of lipid microdomains in mammalian cell membranes, and the potential as well as the limitations of using model systems to help to address such questions.