Angioimmunoblastic T-cell lymphoma (AITL), the second most common peripheral T-cell lymphoma (PTCL) entity, encompasses distinct clinical and pathological features and often manifests with symptoms reflective of immune dysfunction. The pathological spectrum of AITL is broad; the tumor cells are typically outnumbered by a reactive cellular infiltrate comprising non-neoplastic small lymphocytes, Epstein-Barr virus (EBV)-infected large B cells, eosinophils, plasma cells, histiocytes, arborizing vessels, and follicular dendritic cells (FDCs). The recent identification of follicular helper T (TFH) cell as the cell of origin of this neoplasm represents a major step in our understanding of the pathobiological characteristics of the disease. Several markers of normal TFH cells have been recently validated for use in diagnostic pathology practice as they represent useful adjuncts to AITL identification. Yet the genetic alterations underlying AITL pathogenesis are still poorly understood. Deciphering the pathogenesis of the disease is needed to identify targets for new therapies that are expected to improve the poor outcome of AITL patients, when treated with conventional chemotherapy regimens. In this respect, efforts will be needed to evaluate promising innovative therapies in prospective clinical trials.