Inclusion Criteria:

1. Patients with MDS and >/= 5% blasts or IPSS risk intermediate or high; patients with CMML.
2. No prior intensive chemotherapy or high-dose ara-C (>/= 1g/m2).
3. Prior biologic therapies, targeted therapies, or single agent chemotherapy allowed.
4. Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease.
5. Hydroxyurea is permitted for control of counts prior to treatment.
6. Procrit, GCSF are allowed before therapy.
7. Performance 0-2 (ECOG). Adequate organ function including the following:Adequate liver function (bilirubin of < 2mg/dl), and renal function (creatinine < 2mg/dl), and SGPT (ALT) < 3 X ULN. Adequate cardiac functions (NYHA cardiac III-IV excluded).
8. Signed informed consent.

Exclusion Criteria:

1. Nursing and pregnant females. Patients of childbearing potential should practice effective methods of contraception. Child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
2. Active and uncontrolled infections.
3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
4. Prior clofarabine treatment.