Integral membrane proteins are defined as proteins that span the membrane at least once. Until now, hundreds of coding sequences have been obtained for integral membrane proteins, but by contrast only a limited amount of information about the atomic structure of detergent solubilized proteins has been reported. So far, four kinds of structures have been observed for integral membrane proteins whose structures have been determined either by X-ray crystallography or electron crystallography. The structures known with high resolution are the photo-synthetic reaction centers, the porins, bacteriorhodopsin, and the light harvesting complex II. Determination of these three-dimensional (3-D) structures has provided the information upon which the extensively used prediction methods for the arrangement of membrane proteins have been based. In the absence of three-dimensional structure information, computational methods based on the analysis and comparison of amino-acid sequences have been used to predict the topology of membrane proteins. These methods give a two-dimensional picture of the arrangement of the protein in the membrane. In the meantime, new experimental procedures have been developed, increasing the possibilities to probe membrane topology, and thus the validity of the computational methods.