Since their introduction to the clinic some 30 yr ago, interferons (IFNs) have become standard therapy for a range of disorders, including malignant and benign tumors as well as various viral diseases. Although IFNs will induce remissions in some patients with cancer, they are of no benefit or, at best, lead only to minor improvements in the great majority of patients with malignant disease. One of the great challenges of IFN research is to understand the multiple ways by which IFNs influence the behavior of tumor cells and to identify the factors that underlie the resistance of some tumors to IFNs. This reviews is written with a focus on two anticellular effects of IFN, inhibition of proliferation and induction of apoptosis, possible mechanisms underlying the antitumor action of IFN. In addition, possible reasons for IFN tumor cell resistance are also discussed.