Mycoparasitism is a lifestyle where one fungus establishes parasitic interactions with other fungi. Species of the genus Trichoderma together with Clonostachys rosea are among the most studied fungal mycoparasites. They have wide host ranges comprising several plant pathogens and are used for biological control of plant diseases. Trichoderma as well as C. rosea mycoparasites efficiently overgrow and kill their fungal prey by using infection structures and by applying lytic enzymes and toxic metabolites. Most of our knowledge on the putative signals and signaling pathways involved in prey recognition and activation of the mycoparasitic response is derived from studies with Trichoderma. These fungi rely on G-protein signaling, the cAMP pathway, and mitogen-activated protein kinase cascades during growth and development as well as during mycoparasitism. The signals being recognized by the mycoparasite may include surface molecules and surface properties as well as secondary metabolites and other small molecules released from the prey. Their exact nature, however, remains elusive so far. Recent genomics-based studies of mycoparasitic fungi of the order Hypocreales, i.e., Trichoderma species, C. rosea, Tolypocladium ophioglossoides, and Escovopsis weberi, revealed not only several gene families with a mycoparasitism-related expansion of gene paralogue numbers, but also distinct differences between the different mycoparasites. We use this information to illustrate the biological principles and molecular basis of necrotrophic mycoparasitism and compare the mycoparasitic strategies of Trichoderma as a "model" mycoparasite with the behavior and special features of C. rosea, T. ophioglossoides, and E. weberi.