Lymphadenitis refers to any condition that results in an inflamed lymph node or group of lymph nodes. A careful medical history and physical examination are important when suspecting the diagnosis. Although infection is the most common cause of inflamed lymph nodes, noninfectious etiologies should also be considered. The history of the present illness, including the length of time the symptoms have been present, along with any associated systemic signs or symptoms can provide important clues about the underlying cause. A history of exposure to an infectious agent known to cause lymphadenitis and physical examination findings related to the anatomic location(s) of the affected lymph nodes can also be very useful in narrowing the broad differential diagnosis. By far, the most common causes of acute bacterial lymphadenitis are Staphylococcus aureus and Streptococcus pyogenes. As a group, subacute and chronic lymphadenitis is less common than acute infection but carries a much broader differential diagnosis with Epstein–Barr virus, cytomegalovirus, nontuberculous mycobacteria, and Bartonella henselae, the cause of cat scratch disease, becoming the primary considerations. While tuberculosis (TB) is generally considered an infection of the lungs, one of the well-described clinical presentations of extrapulmonary TB is chronic lymphadenitis. Less common microbiologic causes of lymphadenitis include other bacteria, viruses, several fungi, and at least one parasite. Acute lymphadenitis is usually treated empirically with antimicrobial agents effective against S. aureus and S. pyogenes, but material draining from a suppurative lymph node should be cultured to optimize definitive anti-infective therapy. When the illness is atypical, prolonged, or severe, a diagnostic evaluation that includes blood tests, imaging studies, and screening for TB should be performed. If the diagnosis remains enigmatic despite those efforts, fine needle aspiration, lymph node biopsy, or complete surgical excision of the inflamed lymph node may be necessary. Surgically obtained tissue should be sent for microbiologic studies and histologic evaluation. Definitive medical treatment depends on the identified underlying cause.