Calmodulin (CaM) is a protein capable of recognizing positively charged, amphiphilic alpha-helical peptides independent of their precise amino acid sequences; this structural feature has also been found in many CaM-binding proteins. Recent work involving crystallography and site-directed mutagenesis of CaM along with studies of photoreactive and fluorescent CaM-binding peptides have helped define how calmodulin interacts with amphiphilic helices.