Membrane proteins, although constituting about one-third of all proteins encoded by the genomes of living organisms, are still strongly underrepresented in the database of 3D protein structures, which reflects the big challenge posed by this class of proteins. Novel and fundamental insights into the structure, function, assembly and interaction with lipids of membrane proteins are continuously revealed by structural biologists employing electron and x-ray approaches. To date, two structural motifs, α-helices and β-sheets, have been found in membrane proteins and interestingly these two structural motives correlate with the location: while α-helical bundles are most often found in the receptors and ion channels of plasma and endoplasmic reticulum membranes, β-barrels are restricted to the outer membrane of Gram-negative bacteria, the mitochondrial membrane and chloroplasts and represent the structural motif used by several microbial toxins to form cytotoxic transmembrane channels. The β-barrel, while being a rigid and stable motif is a versatile scaffold, having a wide variation in the size of the barrel, in the mechanism to open or close the gate and to impose selectivity on substrates. The difficulty in obtaining crystals suitable for high-resolution studies of outer membrane proteins has resulted in their under-representation in the Protein data Bank . Even if the number of x-ray structures of integral membrane proteins has greatly increased in recent years, only a few of them provide information at a molecular level on how proteins interact with lipids that surround them in the membrane. The detailed mechanism of protein lipid interactions is of fundamental importance for understanding membrane protein folding, membrane adsorption, insertion and function in lipid bilayers. Both specific and aspecific interactions with lipids may participate in protein folding and assembly.