The decay-accelerating factor (DAF, CD55) physiologically serves as an inhibitor of the complement system. Moreover, DAF is broadly expressed in malignant tumors. Here, DAF seems to dispose of several different functions reaching far beyond its immunological role, e.g., promotion of tumorigenesis, decrease of complement mediated tumor cell lysis, autocrine loops for cell rescue and evasion of apoptosis, neoangiogenesis, invasiveness, cell motility, and metastasis via oncogenic tyrosine kinase pathway activation, and specific seven-span transmembrane receptors (CD97) binding. Furthermore, DAF has already been included in diagnostic or therapeutic studies. Thereby, studies applying monoclonal anti-DAF antibodies and anti-DAF vaccination for a targeted therapy have been enrolled recently.