This chapter examines the historical and scientific pursuit of biological explanations for serial homicide, tracing its development from early modern physiognomy through to contemporary neuroscience. Beginning with sixteenth-century traditions that sought to read character from the body, the narrative follows nineteenth-century efforts such as Gall’s phrenology and Lombroso’s theory of the “born criminal,” both of which framed violence as inscribed in anatomy. Early twentieth-century eugenic ideologies extended this logic, embedding heredity into psychiatry and law, while infamous cases such as Peter Kürten and Albert Fish highlighted the inadequacy of purely anatomical or visual markers of criminality. By the mid-twentieth century, advances in genetics and neuroscience shifted the focus toward chromosomal anomalies, neurotransmitter regulation, and traumatic brain injury, reframing violence as the product of biological vulnerability shaped by environment rather than deterministic pathology. Modern neuroscience in the twenty-first century has further expanded this inquiry through neuroimaging, molecular genetics, and studies of gene–environment interactions. Across history, the search to root serial homicidal violence in the body and brain has reflected not only scientific ambition but also cultural anxieties about evil, deviance, and control. Each era’s theories were shaped by its unique intellectual climate, yet all shared the impulse to make the origins of extreme violence visible and measurable. Rather than visual and measurable, however, this chapter shows that contemporary research points to a complex interplay of biology, psychology, and environment, resisting any reduction to a singular biological blueprint.