Cooperation is essential for all domains of life. Yet, ironically, it is intrinsically vulnerable to exploitation by cheats. Hence, an explanatory necessity spurs many evolutionary biologists to search for mechanisms that could support cooperation. In general, cooperation can emerge and be maintained when cooperators are sufficiently interacting with themselves. This communication provides a kind of assortment and reciprocity. The most crucial and common mechanisms to achieve that task are kin selection, spatial structure, and enforcement (punishment). Here, we used agent-based simulation models to investigate these pivotal mechanisms against conditional defector strategies. We concluded that the latter could easily violate the former and take over the population. This surprising outcome may urge us to rethink the evolution of cooperation, as it illustrates that maintaining cooperation may be more difficult than previously thought. Moreover, empirical applications may support these theoretical findings, such as invading the cooperator population of pathogens by genetically engineered conditional defectors, which could be a potential therapy for many incurable diseases.