![][1] ILLUSTRATION: DAVIDE BONAZZI/@SALZMANART The DNA within a human cell, known as the genotype, provides a blueprint to direct a host of processes for building an embodied organism. Although we often treat the human genome as if it is fixed, there is a lot of variation between individuals. The observable human phenotype consists of multiple traits resulting from many genetic variants within any single genome. Hair, eye and skin color, height, build, and behavior all represent such polygenic traits. Many of these traits can be modulated by our environment—for instance, through exposure to stress, sunlight, or microbes—resulting in a range of outcomes. This special issue expands our view of genotype and phenotype and explores recent advances in understanding the factors that influence the development of the human phenotype. We examine cases in which various cells and traits are specified by DNA mutation or epigenetic changes, but we also highlight cases in which phenotype is affected by suites of genes and gene products from commensal bacteria. This special issue illustrates the diverse approaches that together are increasing our understanding of the complex relationship between genotype and phenotype, with the potential to drive discoveries that promote human health. [1]: /embed/graphic-1.gif