Among the most enduring and influential contributions of Nobel Laureate Nikolaas Tinbergen was the introduction of a four-part framework for understanding biological causation. Beyond traditional proximate-mechanistic explanations, Tinbergen asserted, a consideration of both phylogenetic and functional-adaptive perspectives was essential. The application of a framework derived from this Tinbergean structure to human medicine offers a novel approach to the development of theories of causation for high-impact somatic and bio-behavioral disorders. This perspective offers physicians and physicians-in-training an expanded understanding of the nature and origin of human vulnerability to disease. The phylogenetic perspective expands awareness of non-human animals who spontaneously develop the disorder and the functional-adaptive perspective considers what components of vulnerability to disease might have adaptive benefit. Both facilitate the development of novel testable hypotheses.