This review presents recent evidence regarding the adverse effects of antibiotic therapy mediated by collateral damage to commensal flora. Two major drivers have characterized recent research in this field: new perspectives into human microbiota afforded by next-generation DNA sequencing techniques and ongoing attention to antimicrobial resistance. New molecular techniques have illustrated that antibiotic therapy can disturb human microbiota, and that these changes are associated with infection. Concurrently, epidemiologic studies using patient-level data offer new insights into the role of antibiotics in the emergence, selection and spread of antimicrobial resistance, and Clostridium difficile infection (CDI).