The study of cell lineage commitment is critical for improving our understanding of tissue development and regeneration, and for realizing stem cell-based therapies and engineered tissue replacements. Recently, the discovery of an unanticipated degree of variability in fundamental biological processes, including divergent responses of genetically identical cells to various stimuli, has provided mechanistic insight into cellular decision making and the collective behavior of cell populations. Therefore, the study of lineage commitment with single-cell resolution could provide greater knowledge of cellular differentiation mechanisms and the influence of noise on cellular processes. This will require the adoption of new technologies for single-cell analysis as traditional methods typically measure average values of bulk population behavior. This review discusses the recent developments in methods for analyzing the behavior of individual cells, and how these approaches are leading to a deeper understanding and better control of cellular decision making.