We study the behavior of individual cells with a specific focus on “irreversible” cell fate decisions such as apoptosis, senescence, and differentiation. Why do genetically identical cells choose different fates? How much are these decisions controlled by the cell itself and how much is influenced by its environment? We address these questions using a variety of experimental and computational approaches including time-lapse microscopy, single-molecule imaging, computational modeling, and machine learning. Our ultimate goal is to not only understand how cells make decisions under physiological conditions—but to discover how to manipulate these decisions to treat disease.