Synthetic science promises an unparalleled ability to find new meaning in old data, extant results, or previously unconnected methods and concepts, but pursuing synthesis can be a difficult and risky endeavor. Our experience as biologists, informaticians, and educators at the National Evolutionary Synthesis Center has affirmed that synthesis can yield major insights, but also revealed that technological hurdles, prevailing academic culture, and general confusion about the nature of synthesis can hamper its progress. By presenting our view of what synthesis is, why it will continue to drive progress in evolutionary biology, and how to remove barriers to its progress, we provide a map to a future in which all scientists can engage productively in synthetic research. G.G. Simpson (1944) As articulated eloquently by Simpson more than 60-years ago, any attempt to elucidate the history and nature of life from a grand perspective must link clues from different scientific fields and disparate geographic, temporal, and physical scales. ple, Darwin's (1859) fundamental insights came from the union of Malthusian population dynamics, careful observation of artificial selection and natural variation, Smith's economic principles, and geological evidence of the immense age of the Earth. Similarly, the 20th century transformation of biology and the unification of microevolution and macroevolution during the Modern Synthesis resulted from discourse and collaboration between researchers working on heritability, paleontology, development, speciation, Mendelian genetics, natural selection, and systematics (Fisher