In this article, front-line immunosuppressive therapy (IST) for acquired plastic anemia (AA) is illustrated and discussed. Also second-line and salvage options are briefly illustrated. First-line IST should consist of horse anti-thymocyte globulin (ATG) and CsA that has been shown to result in response rates between 60 and 80%. CsA should be given for 12 months until transfusion independence is achieved and then tapered very slowly in the presence of a CR. Patients with a partial response are usually continued on CsA. Tight monitoring of the blood count during CsA tapering is necessary to identify early loss of response. G-CSF 5 μg/kg/day s.c. in the first 30 days has been shown to reduce infections and hospitalization and to identify early responders, as those who achieve neutrophils count of0.5 × 10(9)/L by day +30. This schedule is recommended in the first month of therapy. Afterward, G-CSF can be considered in neutropenic febrile episodes. Patients not achieving transfusion independence after a first course of IST may be considered for second-line IST, or for an allogeneic hematopoietic SCT depending on patient age, ongoing infection, neutrophil count and transfusion requirements. Third-line IST is rarely given, but some options are discussed.