In this review, we summarize approaches to treat cancer with genetically engineered fusion proteins. Such proteins can act as decoy receptors for several ligands or as recruiters of immune effector cells to tumor. Examples of interference with growth factor-mediated tumor growth and tumor-related angiogenesis with fusion proteins consisting of the extracellular domains, and in some cases also of entities of one or several receptors and the Fc part of human IgG1, are discussed. In addition, we present strategies for recruitment of immune effector cells to tumor with fusion proteins. This can be achieved with fusion proteins consisting of a tumor-related antibody and a cytokine or major histocompatibilty complex class-I-peptide complexes, by T-cell receptor cytokine fusion proteins or by combination of a T-cell-recruiting antibody with a tumor-related ligand or a defined T-cell receptor.