Diarrheal illness caused by bacterial pathogens is a global health problem and remains one of the most common complaints prompting patients to seek medical care. Strategies to increase the yield of stool culture and new rapid diagnostic tests can improve diagnostic ability. Emerging antimicrobial resistance among the common bacterial causes of diarrhea has made treatment more challenging. Emerging fluoroquinolone resistance is a particular concern. Recent studies of rifaximin, a nonabsorbed antibiotic for the treatment of bacterial diarrhea, have shown favorable results. Rifaximin may represent a much-needed addition to the armamentarium against bacterial agents.