Inclusion Criteria:

• Diagnosis of 1) AML (WHO classification definition of > 20% blasts), or 2) high risk MDS (defined as the presence of > 10% blasts).
• Patients aged 15 to 60 years are eligible. Patients older than 60 who are deemed fit to receive intensive chemotherapy by the treating physician are eligible after discussion with the PI. For the Phase II portion of the study, patients must be chemo-naïve, i.e. not have received any prior chemotherapy (except hydrea) for AML or MDS. They could have received hypomethylator agents, transfusions, hematopoietic growth factors or vitamins.

Temporary prior measures such as pheresis or hydrea are allowed. In the Phase I portion, patients with relapsed or refractory AML/MDS are also eligible.

• Serum biochemical values with the following limits unless considered due to leukemia: 1) creatinine less than or equal to 2 mg/dl, 2) total bilirubin less than or equal to 2 mg/dL, unless increase is due to hemolysis or congenital disorder, and 3) transaminases (SG PT) less than or equal to 2.5x ULN
• Ability to take oral medication.
• Ability to understand and provide signed informed consent.
• Baseline test of ejection fraction must be >/=50%.
• Performance status < 3, unless directly related to the disease process as determined by the principal investigator.

Exclusion Criteria:

• Patients with APL.
• Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results.
• Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (such as birth control pills, IUD, diaphragm, abstinence, or condoms by their partner) over the entire course of the study.
• Any significant, uncontrolled hypertension.
• Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. Sorafenib is contraindicated in patients with known severe hypersensitivity to sorafenib or any of the excipients.
• Known human immunodeficiency virus (HIV) infection or active Hepatitis B or C.
• Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
• Pulmonary hemorrhage/bleeding event > or = to CTCAE Grade 2 within 4 weeks of first dose of study drug.
• Any other hemorrhage/bleeding event > or = to CTCAE Grade 3 within 4 weeks of first dose of study drug.
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
• Use of St. John's Wort or rifampin.
• Known or suspected allergy to sorafenib or any agent given in the course of this trial.
• Active clinically serious and uncontrolled infection > CTCAE Grade 2
• Serious non-healing wound, ulcer, or bone fracture