A spectrum of biologically different lymphoproliferative diseases is illustrated by the clonal disorders of large granular lymphocytes (LGL). These come from the two subtypes of mature T cells (CD3+) or natural killer (NK) cells (CD3−). Both of them can manifest as either aggressive or indolent disorders. The clinically indolent course is prescribed to the greater number of patients with T-cell LGL leukemia. Their median survival time is >10 years. In more than half of the patients, the symptoms and cytopenias can be managed through immunosuppressive therapy with a low dosage of methotrexate, cyclophosphamide, or cyclosporine A. However, the path is not therapeutic. There have been reports of many cases of an aggressive variant of T-cell LGL leukemia (CD3+CD56+). It is a briskly progressive disorder linked with the Epstein-Barr virus (EBV), with a greater predominance in Asia and South America. The median survival time of the disease is two months, and it is refractory to traditional chemotherapy. A unique EBV-negative virus is chronic NK-cell leukemia or lymphocytosis. It has an indolent clinical course. The subtype’s malignant origin is doubtful because it is tough to deduce the clonality in LGLs of NK-cell origin.