The recent advent of methods for high-throughput single-cell and spatial profiling have opened the way to complete the 150-year-old endeavor of identifying all cell types in the human body, by their distinctive molecular profiles, and to relate this information to other cellular descriptions, physiological phenotypes, molecular mechanisms and functions. Our effort to build a comprehensive reference map of the molecular state of cells in healthy human tissues is propelling the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, provides a framework for understanding cellular dysregulation in human disease, and suggests the possibility of predicting cell types and behaviors, towards a "periodic table of our cells". In this talk, I describe our foundational work underlying single cell genomics and the conceptual framework and impact of our understanding of cell and tissue biology in health, as well as how we use it to shed light on rare disease, cancer, and COVID-19.