Inclusion Criteria:

1. Patients with chronic GVHD following allogeneic HSCT of any source (bone marrow, peripheral blood or cord blood stem cells), from any donor type (related, unrelated, mismatched) and with any type of malignancy.
2. Patients must have failed a trial of steroids and calcineurin inhibitors. Steroids must have been given at an initial dose of 1 mg/kg/d of methylprednisolone (MP) or equivalent in combination with tacrolimus or cyclosporine. Steroid refractoriness or resistance will be defined as: 1- Lack of any response after 1 month of treatment with MP, including 15 days of at least 0.5 mg/kg/d, 2- Worsening of existing GVHD or new organ involvement at any time following one week of initiation of MP at 1 mg/kg/day, 3- Reflare or worsening of GVHD at any time during steroid taper.
3. Patients should not have received any other drug or treatment for chronic GVHD other than steroids and calcineurin inhibitors (i.e. cyclosporine or tacrolimus).
4. ECOG performance status </= 2.
5. WBC >/= 2,500/mm^3, ANC >/= 1,000/mm^3, platelet count >/= 50,000/mm^3
6. Left ventricular ejection fraction >/= 40%. No uncontrolled arrythmias or symptomatic heart disease. FEV1, FVC and DLCO >/= 40%.
7. Serum creatinine <2.0 mg/dL. Serum bilirubin <3 X upper limit of normal, AST (SGOT) and ALT (SGPT) < or = 5 x ULN. No evidence of chronic active hepatitis or cirrhosis.
8. No uncontrolled infections.
9. No evidence of malignancy (patients must be in complete remission from their malignancy)
10. Patients must be able to provide written informed consent, and be 18 years or older at the time of signing consent.
11. Patient must be able to return to clinic for follow up at least every 2 weeks for the first 2 months and at least monthly thereafter.
12. Women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL 10 - 14 days prior to therapy and repeated within 24 hours of starting study drug and must either commit to continued abstinence from heterosexual intercourse or agree to use 2 contraceptive methods. These birth control methods must be used for at least 4 weeks before, during and after lenalidomide therapy. Men must agree not to father a child and agrees to use a condom if his partner is of child bearing potential.
13. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation. (patients intolerant to ASA may use low molecular weight heparin).

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Pregnant or lactating females.
3. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
4. Use of any other experimental drug or therapy within 28 days of baseline.
5. Known hypersensitivity to thalidomide.
6. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
7. Any prior use of Lenalidomide.
8. Use of prior immunosuppressants other than steroids and calcineurin inhibitors (i.e. cyclosporine or tacrolimus).
9. Known positive for HIV or infectious hepatitis, type A, B or C