Here are described the basic mechanisms governing the interactions between proteins and their natural or manmade ligands, together with the principles underlying their analysis. The consequences of these principles are detailed for the simplest case of one-to-one binding. The general features of experimental measurements of biomolecular interactions arise from properties of the molecules involved and, thus, are common to many methods of detection. Consequently, an understanding of these principles greatly simplifies adoption and comparison of experimental methods and provides the rationale underlying many common protocols. In seeking to understand and interpret the results of experiments or identify possible sources of error these fundamental ideas are a constant guide.