In recent medical and popular literature, audiences have been asked to consider whether antibiotics have contributed to the rising obesity epidemic. Prominent magazines have stated that weight may be adversely affected by antibiotics that destroy existing microbiomes and replace them with less helpful ones. However, there is a long history of efforts to investigate the relationship between antibiotics and human weight gain. In the early 1950s, amid initial findings that low doses of antibiotics served as growth promoters in animal livestock, investigators explored the role of antibiotics as magic bullets for human malnutrition. Nevertheless, early enthusiasm was tempered by controlled studies showing that antibiotics did not serve as useful, nonspecific growth promoters for humans. In subsequent decades, against the backdrop of rising concern over antibiotic resistance, investigators studying the role of antibiotics in acute malnutrition have had to navigate a more complicated public health calculus. In a related historical stream, scientists since the 1910s have explored the role of the intestinal microflora in human health. By the 2000s, as increasing resources and more sophisticated tools were devoted to understanding the microbiome (a term coined in 2001), attention would turn to the role of antibiotics and the intestinal microflora in the rising obesity epidemic. Despite scientific and commercial enthusiasm, easy answers (whether about antibiotics or probiotics) have again given way to an appreciation for the complexity of human growth. History encourages caution about our hopes for simplistic answers for presumed "fat drugs" and slimming probiotics alike.