Technology’s role in the fight against malicious cyber-attacks is critical to the increasingly networked world of today. Yet, technology does not exist in isolation: the human factor is an aspect of cyber-defense operations with increasingly recognized importance. Thus, the human factors community has a unique responsibility to help create and validate cyber defense systems according to basic principles and design philosophy. Concurrently, the collective science must advance. These goals are not mutually exclusive pursuits: therefore, toward both these ends, this research provides cyber-cognitive links between cyber defense challenges and major human factors and ergonomics (HFE) research areas that offer solutions and instructive paths forward. In each area, there exist cyber research opportunities and realms of core HFE science for exploration. We raise the cyber defense domain up to the HFE community at-large as a sprawling area for scientific discovery and contribution.