The eukaryotic cell is a bustling collection of macromolecules acting cooperatively to mediate the functions required for cell viability. Specific, context-dependent and tightly controlled physical interactions between these cellular components govern the necessary physiological processes, from cell division to cell death. The specificity, conditionality, and regulation of these binding events depend on communication between the interacting molecules and their surroundings. For proteins, most of this communication is mediated by a variety of modules that are embedded within the protein sequence, can bind a wide array of ligands, and have catalytic, regulatory, or scaffolding activity. These functional units enable proteins to sense, integrate, and transmit environmental and cell state indicators and concomitantly instigate cellular decisions based on the information available to the system.