Membrane proteins are pivotal players in biological processes. In order to understand how a membrane protein works, it is important to purify the protein to fully characterize it. Membrane proteins are difficult to purify because they are present in low levels and they require detergents to become soluble in an aqueous solution. The selection of detergents suitable for the solubilization and purification of a specific membrane protein is critical in the purification of membrane proteins. The aim of this chapter is to provide an overview for the isolation of plasma membranes, selection of detergents for solubilization of membrane proteins, and how the choice of detergents may affect membrane protein purification.