I am here interested in presenting a comparative analysis between the strand of thought known as ‘Degeneration Theory’ and Dostoevsky’s last major novel, The Brothers Karamazov. I will provide a brief contextualization about the influence of Degeneration Theory on Russian thought, postulating that the principal Russian preoccupation concerning degenerate attitudes – above all in Dostoevsky - consists in the disease of moral nihilism. I proceed by outlining the criminal type in The Brothers Karamazov by focalizing my inquiry around the figure of the illegitimate epileptic brother Smerdjakov. My main arguments around the question of social and physiological degeneration will be developed in the subsection devoted to the relationship between poverty and children, whose humility, it is argued, represents Dostoevsky’s answer to the death of God and the moral bankruptcy enacted by nihilistic tendencies. In the third segment I will analyse the maddening outcomes of this disease in my discussion of Ivan Karamazov. Lastly, I will venture into a more unreserved discussion about the purported sequel to The Brothers Karamazov. This study seeks to emphasize the importance in the relationship between characters and the God question, ultimately claiming that for Dostoevsky physical degeneration is deployed as a physiological counterpart for the chief concern of many degenerationist narratives: the spiritual degradation of the individual soul and of the integrity of civilization.