This essay explores how Shakespeare assimilates the confusion among sleeping, dreaming, and waking in key moments in Macbeth as a means of structuring the play and to emphasize sleep’s role in binding together the categories that dissolve over the course of the plot. Early in the play, Lady Macbeth encourages a form of radical wakefulness in her husband common among Shakespeare’s monarchs that enables him to murder the sleeping Duncan and become king himself. Following the murder, however, the restorative sleep both characters long for becomes a curative to which neither has access. The play, in this way, deviates from Shakespeare’s earlier depictions of monarchs afflicted with insomnia by dramatizing the wide-ranging consequences of its effects. The killing of Duncan, this essay suggests, obscures for the Macbeths the boundaries between not only waking and sleeping but also interior and exterior experience. To provide context, this essay consults early modern health manuals that diagnose the deleterious consequences of sleep deprivation that Macbeth manifests as the play progresses.