The use of Nuclear Magnetic Resonance Spectroscopy in Drug Discovery has been routine for several decades. Used independently or in concert with Mass Spectrometry, Isothermal Titration Calorimetry and a variety of Fluorometric assays it allows development of new drug candidates through the use of several pathways. Monitoring ligand-target binding provides a route to screen potential inhibitors for known drug targets. Unfortunately solution NMR encounters a solubility challenge and has a limited applicability to membrane proteins, which have a well-known involvement in key cellular functions and make up 60% of all identified drug targets. For this reason and many others, progress in antimicrobial drug development is slow and the need for new compounds at an all time high with increasing microbial resistance to existing therapeutics. In order to overcome the solubility challenge and mimic the native bilayer environment of the cellular surface a new approach is being developed that permits screening of small compounds against membrane protein drug targets while the protein is in a native-like bilayer. To trap the protein solubilized bilayer we use anodic aluminum oxide (AAO) filters such that solutions containing small molecules can be flowed over the membranes in the AAO pores without dislodging the protein and bilayers. To test this concept we aligned the M2 proton channel from Influenza A virus, a known drug target, in DMPC lipid bilayers within the AAO filters. Selectively 15N site-labeled M2 (residues 22–46) was exposed to various inhibitor compound cocktails while monitoring the very sensitive anisotropic chemical shifts for binding. A flow through cell design is now being developed to semi-automate this screening process.