Theories in personality neuroscience must aim to be consistent with several levels of explanation. If we view personality traits as constructs located only at the psychological level, we must still make their explanations compatible with observations and theories at lower levels, particularly with what we know at the neural level. If we view personality traits as constructs located only at the neural level, we will still need to predict their emergent effects at the psychological level. Personality theory at present treats traits as psychological-level constructs, with even the recent neurally oriented Cybernetic Big Five Theory specified in terms of a “conceptual nervous system” and not requiring complete or immediate translation into neural mechanisms. Here, we argue for the existence of phylogenetically old, neural-level traits that are substantially conserved across many vertebrate species. We first ask what known mechanisms control trait-like properties of neural systems: Focusing on hormones, the GABAA receptor, and amine neurotransmitter systems. We derive from what we know about these sources of neuronal modulation some metatheoretical principles to guide the future development of those aspects of personality theory, starting with neural-level trait constructs and drawing implications for higher-level trait psychology observations. Current descriptive approaches such as the Big Five are an essential precursor to personality neuroscience, but may not map one-to-one to the mechanisms and constructs of a neuroscience-based approach to traits.