Transmembrane proteins can extend across the bilayer as a single α helix, as multiple α helices, or as a rolled-up β sheet (called a β barrel). These transmembrane proteins are amphipathic, having both hydrophobic and hydrophilic regions. Their hydrophobic regions lie in the interior of the bilayer, nestled against the hydrophobic tails of the lipid molecules. Their hydrophilic regions are exposed to the aqueous environment on either side of the membrane.

Some membrane proteins are anchored to the cytosolic half of the lipid bilayer by an amphipathic α helix.

Some proteins lie entirely outside the bilayer, on one side or the other, attached to the membrane by one or more covalently attached lipid groups.

Many proteins are attached to the membrane only by relatively weak, noncovalent interactions with other membrane proteins.