The gastrointestinal (GI) tract has the most extensive exposed surface in the body and is constantly exposed to a wide variety of potentially harmful substances. The GI tract acts as a selective barrier between the tissues of the bird and its luminal environment. This barrier is composed of physical, chemical, immunological, and microbiological components. A wide range of factors associated with diet and infectious disease agents can negatively affect the delicate balance among the components of the chicken gut and, as a result, affect health status and production performance of birds in commercial poultry operations. Phasing out of antibiotic growth promoters from poultry diets in Europe and recent moves toward reduction or removal of these compounds in other parts of the world including North America will likely change the microbial profile of the GI tract environment in commercial poultry. This paper reviews the GI tract from developmental, immunological, and microbial standpoints and then discusses factors that can affect health status of this system. Necrotic enteritis and coccidiosis and their interactions, and possible consequences of antibiotic growth promoter removal from poultry diets with respect to these diseases, are discussed in more detail.