Foodborne illnesses are a substantial health burden in the United States. The Foodborne Diseases Active Surveillance Network (FoodNet) is the principal foodborne disease component of the Centers for Disease Control and Prevention's Emerging Infections Program. FoodNet is a collaborative project among Centers for Disease Control and Prevention, Emerging Infections Program sites, the U.S. Department of Agriculture, and the U.S. Food and Drug Administration. One of FoodNet's main objectives is to monitor changes in the incidence of selected foodborne pathogens. In 1996, FoodNet began active, population-based surveillance for laboratory-diagnosed cases of Campylobacter, Listeria, Salmonella, Shiga toxin-producing E. coli O157, Shigella, Vibrio, and Yersinia infection. Surveillance for cases of Cryptosporidium and Cyclospora infection was added in 1997 and surveillance for non-O157 Shiga toxin-producing E. coli was added in 2000. From 1997 to 2008, the FoodNet surveillance population increased, primarily through the addition of new sites. The increase in the number of FoodNet sites and the size of the population under surveillance as well as the variation in the incidence of infections among sites posed challenges in the selection of the most appropriate method to monitor changes in incidence. To account for variation introduced by changes in population size, a main-effects, log-linear Poisson (negative binomial) regression model was adopted to estimate the magnitude of changes in the incidence of pathogens by comparing current year incidence to reference periods. The article explains how FoodNet uses the negative binomial model to examine changes in incidence over time, describes the reference periods used, explains the graphics used to display results, and discusses future directions in the analysis of trends over time.