Acute diarrheal disease is a frequent primary care reason for consultation, leading to direct and indirect health costs in high-income countries. Most patients presenting with acute diarrhea will have a favorable clinical course with just a symptomatic treatment. The challenge for the general practitioner is to identify the patients who need paraclinical exams and/or antibiotics. Molecular identification of pathogens in stool samples has developed over the past years and presents both advantages and limitations. Because of increasing microbial resistance to quinolones in Campylobacter and Shigella strains, azithromycin is now the first choice for an empiric antimicrobial therapy. This article will discuss these latest developments in the management of acute diarrhea in the primary care setting.