Presumably diverse cases are at present lumped under the heading peripheral T-cell lymphoma, not otherwise categorized, or unspecified (PTCL-U), which comprise the largest group of T-cell neoplasms in Western countries. Although a variety of morphologic subtypes have been described, no consistent immunophenotypic, genetic, or clinical features have been associated with most of them. Hopefully, some progress can be expected from the novel sophisticated and powerful genomic and proteomics technologies, which may uncover the group of T-cell neoplasms, and perhaps identify some specific disease entities. An improved understanding of their biology may improve our ability to develop better treatments for these disorders. Indeed, these disorders are among the most aggressive lymphomas, representing a wide variety of infrequent clinicopathologic syndromes that share a dismal prognosis. The treatments used for diffuse large B-cell lymphoma have produced disappointing results in peripheral T-cell lymphoma. Clinical trials focusing specifically on these subtypes are therefore warranted. Novel strategies need to be developed and specific regimens including active agents in peripheral T-cell lymphoma should be investigated. This effort will be successful only if a large international collaboration can be set up because of the rarity of most subtypes.