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Selection regimes and population structures can be powerfully changed by domestication and feralization, and these changes can modulate animal fitness in both captive and natural environments. In this review, we synthesize recent studies of these two processes and consider their impacts on organismal and population fitness. Domestication and feralization offer multiple windows into the forms and mechanisms of maladaptation. Firstly, domestic and feral organisms that exhibit suboptimal traits or fitness allow us to identify their underlying causes within tractable research systems. This has facilitated significant progress in our general understandings of genotype-phenotype relationships, fitness trade-offs, and the roles of population structure and artificial selection in shaping domestic and formerly domestic organisms. Additionally, feralization of artificially selected gene variants and organisms can reveal or produce maladaptation in other inhabitants of an invaded biotic community. In these instances, feral animals often show similar fitness advantages to other invasive species, but they are also unique in their capacities to modify natural ecosystems through introductions of artificially selected traits. We conclude with a brief consideration of how emerging technologies such as genome editing could change the tempos, trajectories, and ecological consequences of both domestication and feralization. In addition to providing basic evolutionary insights, our growing understanding of mechanisms through which artificial selection can modulate fitness has diverse and important applications-from enhancing the welfare, sustainability, and efficiency of agroindustry, to mitigating biotic invasions.