The human genome encodes thousands of proteins that are crucial for life. These proteins function by interacting with a variety of targets, including other proteins, nucleic acids, carbohydrates, lipids, metabolites, small molecules, metals, etc. For more than a century, researchers have been attempting to understand the nature of these protein-ligand interactions and how they regulate cellular events. While today's scientific literature contains thousands of articles devoted to protein-ligand interactions (searching PubMed with the term protein interactions yields >250 000 articles), the majority of these studies focus on high affinity complexes (typically with a KD<10-6M) that are readily detectable and, therefore, amenable to a variety of techniques for analysis. This article is protected by copyright. All rights reserved.