Modern conversations between the natural sciences and theology on the human soul have not so far engaged extensively with relevant debates in the early church. Contemporary neuroscience tends to operate within a monistic paradigm, often referred to as ‘physicalism’, that understands human mental activity entirely in naturalistic terms. While there is ongoing scientific debate about the degree to which human consciousness can be reduced entirely to biology, physicalism is often cited as making traditional religious belief in the soul obsolete, or at least modifying it significantly. The Apollinarian question of whether Jesus has a soul therefore reappears. This article considers the contemporary relevance of the Apollinarian controversy, suggesting that fourth-century insights possess key points of contact with the modern non-reductive physicalist position and thus raising important considerations for the science-theology conversation on the soul.