Proteomic analysis of organelles or specific groups of proteins is a potentially powerful strategy for the discovery of proteins that are involved in specific cellular functions or disease. Targeted enrichment of specific groups of proteins or subcellular organelles reduces the complexity of samples and simplifies such approaches. The subset of cellular proteins that is associated with plasma membranes is of high biological importance. The plasma membrane delineates the cell and provides a physical boundary between the cell and its environment. Plasma membrane proteins play important roles in cell–cell interactions, material transport, and signal transduction. Integral and peripheral membrane proteins e.g., G-protein coupled receptors (GPCRs), receptors for growth factors and cytokines, receptor-associated signaling proteins, and ion-channels are major focuses for new drug targets.