Intense human persecution of wildlife in the past selected for shy individuals that survived in suboptimal refuge habitats. It appears that this long-term conflict is coming to an end in southern Europe, where direct persecution of wildlife has dramatically decreased due to human abandonment of the rural world and an increase in respectful attitudes toward wildlife. We provide a number of empirical examples of ongoing ‘refuge abandonment’ and the expansion of fearless behavior among southern European wildlife, including island and mainland case studies as well as predator and prey examples. We predict that many ecological refugees will increasingly abandon their historical refuges (of which many currently coincide with protected areas), and that the frequency of fearless behaviors will increase via cultural habituation and natural selection in populations of mammals and birds that were formerly persecuted. We also suggest that this has been a nonlinear process, which began considerably earlier than it became evident, with a long latent inertial regime, and a relatively rapid transition to a state of refuge abandonment and occupation of new, more anthropogenic habitats. The process of refuge abandonment and expansion of fearless behaviors will bring a new paradigm regarding human– wildlife relationships. It will also force changes in policies to protect high-quality sites that are currently unoccupied and unprotected. Refuge abandonment may form a completely new research agenda and should be taken into account when studying patterns of wildlife dispersal or dynamics of spatially structured populations, among other relevant topics.