Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.
2. Age >/= 18 years at the time of signing the informed consent form. (Revlimid has not been tested in younger patients)
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Diagnosis of relapsed/refractory AML (other than APL) or high-risk MDS (IPSS categories intermediate-2 and high) with chromosome 5 abnormality as a sole abnormality or with additional abnormalities. MDS patients with blast percentage of >/= 10% will be considered high-risk.
5. All non-hematological toxicity of previous cancer therapy should have resolved to </= grade1 (except alopecia or other toxicities not involving major organs).
6. Should not have received any prior treatment for AML or MDS within 2 weeks of starting Revlimid. Use of hydrea to control proliferative disease will be allowed prior to starting Revlimid and for 7 days during cycles 1 and 2 (Maximum daily dose of 7gm).
7. ECOG performance status of </ =2 at study entry
8. Laboratory test results within these ranges: • Serum creatinine </= 1.5 mg/dL • Total bilirubin </=1.5 mg/dL • AST (SGOT) and ALT (SGPT) </=2 x ULN or </=5 x ULN if related to disease
9. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing Revlimid (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking Revlimid. FCBP must also agree to ongoing pregnancy testing.
10. (continued from above) Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
11. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
12. Disease free of prior malignancies for >/ = 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast.

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 breast feeding females. (Lactating females must agree not to breast feed while taking Revlimid).
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 experimental 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 Revlimid.
8. Concurrent use of other anti-cancer agents or treatments. (Use of hydrea permitted as indicated in inclusion criterion 6)
9. Known positive for HIV or infectious hepatitis type B or C.
10. Heart rate less than or equal to 50.