Visions of a synthetic engineering-based approach to biology have been a prominent and recurring theme in the history of biology in the twentieth century. Several major moments in this earlier history of attempts to redesign life are discussed: the turn-of-the-century prominence of experimental evolution and the coining of “synthetic biology” in 1912; early synthetic approaches to experimentally investigating the historical origin of life on the early earth; the goal of developing a “technology of the living substance” and the creation of life in the test tube as the ultimate epistemic goal for an engineered biology; the creation of synthetic new species in the first explicitly labeled efforts at “genetic engineering” in the 1930s; and the re-emergence of “synthetic biology” during the rise to prominence of novel recombinant DNA technology in the 1970s. The use of synthesis as a both mode of inquiry and of construction is highlighted. Aspects of the more recent history (the last decade) of contemporary synthetic biology are also explored.