In the context of drought and increasingly severe water shortages, agriculture faces a major challenge in continuing to feed a growing global popula tion. Irrigation of crops with treated municipal wastewater can contribute to meeting agriculture's water needs. However, the use of treated wastewater carries numerous public health risks due to the presence of various human and animal pathogens including spore-forming Clostridium species, such as Clostridioides difficile and Clostri dium perfringens. Antibiotic resistance in these important pathogens is an emerging issue. Spores of these bacteria are extremely persistent, and they can persist for years in a wide range of environments. Their presence in treated wastewater could lead to contamination of soil and of plant-based foods grown for human or animal consumption. Within this context, the present review addresses the pathogenicity of C. difficile and C. perfringens and their potential role in the dissemination of antimicrobial resistance in the context of wastewater reuse for agriculture.