Interferon-A (IFN-A) is an effective agent in the treatment of chronic myelogenous leukemia (CML). Hematologic remissions occur in the majority of patients with newly diagnosed disease, and cytogenetic remissions may occur in up to 50% of patients. Several studies have shown a correlation between the dose of IFN-A and achievement of a major cytogenetic response; this response has also been correlated with prolonged survival. However, IFN-A may be associated with significant side effects that reduce enthusiasm for the use of this drug, produce difficulties in patient compliance, and limit the dose delivered to the patient, thus resulting in ineffective use of IFN-A. Experience with this drug has led to a refinement in techniques for initiation of therapy as well as interventions to deal with side effects. These strategies are often not discussed in publications dealing with response rates and survival. In this review we discuss strategies to minimize toxicity and improve the effectiveness of IFN-A in the treatment of CML.