Clostridioides difficile and norovirus are common causes of healthcare-associated gastroenteritis and both organisms cause outbreaks in pediatric healthcare settings. The spores are resistant to routine environmental cleaning with detergents and can survive in the environment for months. C. difficile can easily be transmitted on the hands of healthcare workers, either from direct patient care activities or through contact with a contaminated environment. Norovirus is highly contagious, with an estimated infectious dose as low as 18 viral particles. Transmission occurs either person-to-person or through ingestion of contaminated food and water. This chapter outlines strategies to prevent transmission of healthcare-associated C. difficile and norovirus infections. It includes recommendations for surveillance, isolation, hand hygiene, environmental cleaning and removal of isolation precautions. Diagnostic methods are reviewed, highlighting the challenge of distinguishing between colonization and clinically significant C. difficile infection in young children.