Imatinib mesylate and perifosine are two relatively new drugs that have improved outcomes for patients with gastrointestinal stromal tumors in recent years. The ocular side effects of these two drugs are discussed in this chapter. The most common ocular side effect associated with imatinib mesylate is periorbital edema. Perifosine has been associated with a ring-shaped perilimbal corneal ulceration that can be treated with topical steroids and topical antibiotics.