Antibiotics are the main, and often only, clinical intervention for prophylactic and active treatment of bacterial infections in humans. Perhaps it is not surprising that these drugs also shift the composition of commensal bacteria inside our bodies, especially those within the gut microbial community (microbiota). How these dynamics ultimately affect the function of the gut microbiota, however, is not fully appreciated. Likewise, how antibiotic induced changes facilitate the outgrowth and pathogenicity of certain bacterial strains remains largely enigmatic. Here, we discuss the merits of a microbial ecology approach toward understanding a common side effect of antibiotic use, antibiotic-associated diarrhea (AAD), and the opportunistic bacterial infections that sometimes underlie it. As an example, we discuss how this approach is being used to address complex disease dynamics during Clostridium difficile infection.