Plasma and serum have been the focus of intense study in recent years in the expectation that they will provide important biomarkers of health and disease, without the need for invasive procedures. This aim has been hindered by the fact that a few highly abundant proteins dominate the protein profile, masking the lower abundance proteins and limiting our ability to analyse the entire plasma proteome. This chapter details a simple and effective method for removal of two of the most dominant proteins in plasma, albumin and immunoglobulin.