Along alternative protective pathways, human cells can synthesize biologically active proteins that interfere with HIV replication, but are not viral antigen specific. HIV is sensitive to several viral inhibitors of cellular origin, such as interferons or interferon-regulated proteins. With the progress of AIDS research it has become evident that the immune cells of some individuals are capable of restricting the virus by secretion of other, yet unidentified factor(s) that can be detected only by their potent antiviral activity. Research efforts to identify this inhibitor of HIV ? a ?magic bullet' released by our immune cells ? have revealed the identity of several novel molecules and added to the knowledge of innate cellular responses to viral invasion.