Most work describing the histopathology of normal human thymus has focused on pediatric thymus because of tissue availability and high thymopoietic activity. However, pathologic examination of the thymus can provide information about immune status that is relevant to the clinical care of patients of all ages. Understanding age-related changes in the relative abundance and composition of anatomic compartments within the thymus is critical for evaluation of the thymus in normal adults and patients with diseases that affect the thymus. The purpose of this review is to acquaint diagnostic pathologists with some of the newer histologic, flow cytometric, and molecular techniques for assessment of non-neoplastic thymus. Diagnostic criteria are presented for assessment of thymic function and for determining the mechanisms underlying thymic hyperplasia. Accurate assessment of thymic function is critical for the diagnosis and treatment of patients with complete DiGeorge syndrome and can complement the clinical care of patients with a variety of disorders that affect the immune system.