It is over 50 years since the discovery of aflatoxins focused the attention of food safety specialists on fungal toxins in the feed and food supply. Since then, analysis of this important group of natural contaminants has advanced in parallel with general developments in analytical science, and current MS methods are capable of simultaneously analyzing hundreds of compounds, including mycotoxins, pesticides, and drugs. This profusion of data may advance our understanding of human exposure, yet constitutes an interpretive challenge to toxicologists and food safety regulators. Despite these advances in analytical science, the basic problem of the extreme heterogeneity of mycotoxin contamination, although now well understood, cannot be circumvented. The real health challenges posed by mycotoxin exposure occur in the developing world, especially among small-scale and subsistence farmers. Addressing these problems requires innovative approaches in which analytical science must also play a role in providing suitable out-of-laboratory analytical techniques.