When investigation of the biology of cells coalesced as a field more than fifty years ago, the focus was on discovery of the internal structures of cells. Now that we have sequenced the complete human genome, we are identifying disease-associated genes. The challenge is to determine how genes and gene products function in human health and disease. The workings of the cell remain at the very heart of these investigations. Moreover, as science, technologies, and medicine evolve, boundaries between disciplines are disappearing and investigation of cell biology has become increasingly integrated. We are expanding our knowledge of cellular mechanisms through collaborations with physical/computational scientists, engineers, biochemists, immunologists, geneticists, clinicians and other bioscientists. Multidisciplinary integration is enabling us to address greater challenges, ranging from single-cell interactions to multicellular organization, and to apply these discoveries to human physiology and improvement of human health.