Hebrews 6:4–6 is regularly identified as a challenge to the doctrine of perseverance. This study presents a history of Reformed interpretation of Hebrews 6:4–6 with particular focus on the question of the doctrine of perseverance and the identity of those described in this passage. It also traces the reception of John Owen and his interpretation of that passage within the English history of interpretation. Owen (1616–1683) is significant to this history because he stands as a prominent early figure of the Reformed tradition, and his Exposition on Hebrews is a massive and thoughtful contribution to the body of interpretive literature on Hebrews in the English-speaking world. Later Reformed biblical interpreters are grouped and analysed within their hermeneutical, theological, and exegetical contexts. Critically adopting the methodology of reception history as presented by Parris and Evans, these later interpretations of Hebrews 6:4–6 are examined with the intent of discerning to what extent Owen’s interpretation of this passage is formative on later readings in terms of continuity, rebuttal, and modification, and for how long and in what ways. This is the first study to examine the influence of John Owen’s work on Heb 6:4–6 on later Reformed exegetes. It finds that within the history of interpretation, most Reformed interpreters have declined to see the descriptive markers of Heb 6:4–5 as denoting genuine Christians. Earlier interpreters instead tended to regard the markers in a negative light and to emphasise how they fell short of describing a state of salvation. However, a trend began with Owen to see these markers in a positive light. While not denoting salvation, these were instead understood to be designed to demonstrate how much these people had experienced. This broad position characterised all Reformed interpretations until the early nineteenth century. From this point, a consistent minority tradition of dissent began which held that Heb 6:4–6 did indeed describe true Christians, and adopted different strategies which nevertheless left the doctrine of perseverance intact. Much of Owen’s influence on this interpretive history has been concentrated around the interpreters who have foregrounded the theological and pastoral purposes of Scripture. This itself has been aligned with acceptance of the majority Reformed position on Heb 6:4–6 and with the fortunes of theologically-oriented interpretation through the past three centuries. Owen’s influence has been uneven, with varied redeployment of his exegetical choices and interpretive moves found within the work of appreciative interpreters. Reasons for any of these interpreters adopting, rejecting, or ignoring any given feature(s) of Owen’s interpretation cannot usually be known for certain. However, explanations for his irregular reception are likely linked to the shifting expectations of biblical interpretation, the changing importance given to the question of perseverance, and to the onerous size of Owen’s Exposition. This study concludes that while Owen’s work on Hebrews, including 6:4–6 specifically, has retained a substantial amount of general esteem, his actual impact on later interpretations of Heb 6:4–6 has been more limited.