Therapy with a purine analogue (cladribine or pentostatin, most often cladribine) has revolutionized the care of patients with hairy cell leukemia, resulting in very long-lasting remissions in the majority of cases. For patients who relapse, re-induction with cladribine again induces durable remissions. For patients with short remission durations, rituximab can be effective, and for a small proportion of patients with more resistant disease, BL22 has been used successfully. I report three cases in which alpha interferon induction and maintenance has produced ongoing remissions in patients with short remission durations after cladribine. One patient had also not responded to rituximab. Alpha interferon may be a very effective treatment option for selected patients with relapsed hairy cell leukemia.