Foods are complex mixtures of lipids, carbohydrates, proteins, vitamins, organic compounds, and other naturally occurring substances. Sometimes added to this mixture are residues of pesticides, veterinary and human drugs, microbial toxins, preservatives, contaminants from food processing and packaging, and other residues. This milieu of compounds can pose difficulties in the analysis of food contaminants. There is an expanding need for rapid and cost-effective residue methods for difficult food matrixes to safeguard our food supply. Bioanalytical methods are established for many food contaminants such as mycotoxins and are the method of choice for many food allergens. Bioanalytical methods are often more cost-effective and sensitive than instrumental procedures. Recent developments in bioanalytical methods may provide more applications for their use in food analysis.