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The discovery of antibiotics and their subsequent therapeutic use revolutionized our ability to treat once deadly infectious diseases, and antibiotics have become one of the most commonly prescribed drug classes. Unfortunately, these compounds not only target pathogenic strains, but also non-pathogenic bacteria that fulfill important functions for the human host. As such, antibiotic treatment can cause severe collateral damage, resulting in dysbiosis, for example, in the human gut microbiome. Given the immense importance of the gut microbiome for human health, antibiotic-induced dysbiosis can cause a variety of detrimental health outcomes. In addition, antibiotic (over-)use causes selection of antibiotic-resistant strains, and the human gut microbiome has become a major reservoir for resistance determinants that can transfer to pathogenic isolates and cause hard-to-treat infections. In this review, we describe various adverse effects that antibiotic use has on the human gut microbiome, how we can approach this problem experimentally, and discuss pathways to mitigate antibiotic-induced collateral damage.