The examination of a series of trifluoromethyl ketone inhibitors of Fatty Acid Amide Hydrolase (FAAH, oleamide hydrolase, anandamide amidohydrolase) is detailed in efforts that define structural and conformational properties that contribute to enzyme inhibition and substrate binding. The results imply an extended bound conformation, highlight a role for the presence, position, and stereochemistry of a delta cis double bond, and suggest little apparent role for C11-C18/C22 of the fatty acid amide substrates.