• To determine the safety and maximally tolerated dose of sunitinib plus erlotinib in patients with non-small cell lung cancer (NSCLC).
• To determine response to sunitinib plus erlotinib in patients with non-small cell lung cancer.

Inclusion Criteria:

• Histologically or cytologically proven stage IIIB (with pleural effusion or pericardial effusion) or IV (either primary or recurrent) NSCLC (except squamous cell histology).
• Measurable disease per RECIST
• Life expectancy of at least 12 weeks.
• Adequate bone marrow, hepatic and renal function
• ECOG performance status 0, 1 or 2.
• One and only one prior treatment with a chemotherapy regimen, including a platinum based regimen for advanced disease (Stage IIIB with malignant effusion or Stage IV).
• Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
• Female patients must be surgically sterile, postmenopausal or agree to use effective contraception during the period of therapy. Male patients must be surgically sterile or agree to use effective contraception during the period of therapy.

Exclusion Criteria:

• Squamous cell histology.
• History of untreated brain metastases
• Prior treatment with >1 systemic chemotherapy-based regimens for advanced disease (Stage IIIB with malignant effusion or Stage IV).
• Prior treatment with any receptor tyrosine kinase inhibitors, VEGF inhibitors, or other angiogenic inhibitors (including but not limited to bevacizumab, sunitinib, erlotinib, gefitinib, or thalidomide).
• Prior chemotherapy, radiation therapy, surgery, or investigational agent within 4 weeks prior to study entry, except palliative radiation therapy to a non-target lesions (must have been completed 2 weeks prior to study enrollment).
• Eligibility of patients receiving any medications or substances known to induce or inhibit CYP3A4 and /or with the potential to affect the activity or pharmacokinetics of sunitinib or erlotinib will be determined following review of their case by the Principal Investigator.
• NCI CTCAE grade 3 hemorrhage within 4 weeks of starting therapy.
• Ongoing treatment with warfarin
• Prior treatment with high-dose chemotherapy requiring stem cell rescue.
• Prior irradiation to >25% of the bone marrow (whole pelvis = 25%).
• Diagnosis within prior 3 years of second malignancy, except basal cell carcinoma, squamous cell skin carcinoma or in situ carcinoma that has been completely treated without evidence of recurrent disease for 12 months.
• Current treatment on another therapeutic clinical trial or receipt of another investigative agent within 4 weeks of study entry.
• Any of the following within 12 months prior to starting study treatment: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus.
• Hypertension (>150/100mmHg) that cannot be controlled with standard antihypertensive agents.
• Ongoing cardiac dysrhythmias of grade >2, ≥ grade 3 atrial fibrillation, or QTc interval of >450 msec for males and >470 msec for females.
• Evidence of hemoptysis <4 weeks of starting study treatment.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality
• HIV-positive patients
• Women who are pregnant or breast feeding