Cellular heterogeneity is revolutionizing the way to study, monitor and dissect complex diseases. This has been possible with the technological and computational advances associated to single-cell genomics and epigenomics. Deeper understanding of cell-to-cell variation and its impact on tissue function will open new avenues for early disease detection, accurate diagnosis and personalized treatments, all together leading to the next generation of health care. This review focuses on the recent discoveries that single-cell genomics and epigenomics have facilitated in the context of human health. It highlights the potential of single-cell omics to further advance the development of personalized treatments and precision medicine in cancer, diabetes and chronic age-related diseases. The promise of single-cell technologies to generate new insights about the differences in function between individual cells is just emerging, and it is paving the way for identifying biomarkers and novel therapeutic targets to tackle age, complex diseases and understand the effect of life style interventions and environmental factors.