T-prolymphocytic leukemia (T-PLL) is a rare post-thymic T-cell leukemia characterized by rapidly progressive disease and poor survival rates. Clinical features typical of T-PLL can help differentiate it from other mature T-cell leukemias. Typical findings on the blood film reveal medium sized lymphocytes, with a high nuclear to cytoplasmic ratio. Evidence for optimal treatment is limited to small single-arm studies or retrospective data from tertiary centers with expertise in the management of T-PLL. If a good response is achieved with alemtuzumab upfront, there may be a rationale for retreatment, with one study showing that of 12 patients who were retreated, 5 achieved a second complete response, with one a partial response; however, flow cytometry should be repeated, as T-PLL cells can lose CD52 expression.