Innovative enterosorption strategies for the detoxification of aflatoxins have been developed. Calcium montmorillonite clay (NS) has been shown to prevent aflatoxicosis in a variety of animals when included in the diet. Results have shown that NS clay binds aflatoxins with high affinity and high capacity in the gastrointestinal tract, resulting in a notable reduction in the bioavailability of these toxins without interfering with the utilization of important vitamins and other micronutrients. This strategy is currently being evaluated as a potential remedy for acute aflatoxicosis and as a sustainable intervention for the detoxification of aflatoxin-contaminated food. Clinical intervention trials in the U.S. and Ghana (respectively), have confirmed the apparent safety, efficacy and palatability of NS clay delivered in capsule form and/or in food. A study in Ghanaians at high risk for aflatoxicosis has indicated that NS, at a level equivalent to the minimal effective dose in animals, significantly reduced biomarkers of aflatoxin exposure in blood and urine, and did not interfere with the levels of serum vitamins A and E, and iron and zinc. Ongoing work in the U.S. is focusing on strategies to mitigate dietary risk factors associated with hepatocellular carcinoma. In summary, enterosorption strategies and therapies based on montmorillonite clays are promising for the management of aflatoxins and as a sustainable public health intervention. The montmorillonite clay remedy is novel, inexpensive and easily disseminated. Importantly, all aflatoxin sequestering clays should be rigorously evaluated in vitro and in vivo, and should meet the following criteria: (1) favorable thermodynamic characteristics of mycotoxin sorption, (2) tolerable levels of priority metals, dioxins/furans and other contaminants, (3) safety and efficacy in multiple animal species, (4) safety and efficacy in long-term trials, and (5) negligible interactions with vitamins, iron and zinc and other important micronutrients. Supported by USAID-PCRSP TAM149 and NIH 1R01MD005819-01.