Interferon (IFN)-based therapy, the cornerstone for treatment of hepatitis C virus (HCV) infection, is generally considered to be the single most effective treatment strategy for this infection. Although most adverse effects of IFN therapy respond very well to the cessation of this drug, there are reports of serious irreversible adverse effects. This review article evaluates the adverse effects of IFN therapy in HCV-infected patients. We have undertaken an extensive search for articles regarding IFN and pegylated-IFN (PEG-IFN) therapy and their vascular complications using multiple sources that include PubMed, publishers’ websites, and Google Scholar. The prevalence of ocular disorders in the early period (first 8 weeks) after IFN administration was high with over half of the patients experiencing these adverse effects. Several authors strongly propose screening programs for retinopathy in the early period after IFN administration. Pulmonary hypertension due to IFN therapy is a serious side effect due to its irreversible nature in most patients. Patients who develop signs of acute abdomen up to months after IFN administration should be rapidly assessed for potential adverse effects of IFN. The literature suggests a broad spectrum of vascular injuries to different organs in humans as adverse effects of IFN therapy in HCV-infected patients.