During recent decades, >30 fungal immunomodulatory proteins (FIPs) have been found in a range of mushrooms and other fungi. Various pharmacological functions of FIPs have become important in the discovery and development of new drugs. In this review, we discuss some important factors, focusing on the use of amino acid sequence data to predict structural and physicochemical properties. We also discuss pharmacologic activities and possible mechanisms of the proteins with a focus on antitumor activities. Numerous other questions must also be addressed before FIPs can be widely accepted and used as antitumor agents.