Antibiotics are an essential component of the modern lifestyle. They improve our lives by treating disease, preventing disease, and in the case of agricultural animals by improving feed efficiency. However, antibiotic usage is not without collateral effects. The development and spread of antibiotic resistance is the most notorious concern associated with antibiotic use. New technologies have enabled the study of how the microbiota responds to the antibiotic disturbance, including how the community recovers after the antibiotic is removed. One common theme in studies of antibiotic effects is a rapid increase in Escherichia coli followed by a gradual decline. Increases in E. coli are also associated with systemic host stresses, and may be an indicator of ecosystem disturbances of the intestinal microbiota. Moreover, recent studies have shown additional effects mediated by antibiotics on the gut microbiota, such as the stimulation of gene transfer among gut bacteria and the reduction of immune responses in peripheral organs. Querying the microbiota after antibiotic treatment has led to intriguing hypotheses regarding predicting or mitigating unfavorable treatment outcomes. Here we explore the varied effects of antibiotics on human and animal microbiotas.