Reactive lymphadenopathies often pose a diagnostic problem. The distinction of a reactive from a neoplastic lymph node requires the application of general histologic criteria that traditionally have involved the evaluation of cytologic features including cellular polymorphism v monomorphism and the presence or absence of cytologic atypia. Although these cytologic criteria remain valid, they are not inviolate and exceptions exist that may result in diagnostic ambiguity. In addition, the interpretation of a reactive process in a lymph node is predicated on the evaluation of the dominant histologic architectural pattern and on a systematic approach to the diagnosis. The patterns specifically include whether the nodal architecture is predominantly diffuse, mixed interfollicular and follicular, follicular, or sinusoidal. Under each of these dominant architectural configurations, a host of benign reactive diagnoses may be assigned. An awareness of the various diagnostic categories for each major histologic pattern, the range and subtleties of their histologic expression, and the application of new methods, such as immunology to determine clonality, have resulted in simultaneous narrowing of the diagnostic possibilities and expansion of our comprehension of the reactive lymphadenopathies.