This study examines the casuistry of William Perkins in order to reconcile differing contemporary representations of the puritan tradition. These differing conceptions centered on whether puritan doctrine produced comfort, or despair. Puritan divines acknowledged that despair was a serious issue among their flock, and the varied works read and composed by the godly indicate a sustained engagement with despair, which was often precipitated by uncertainty over the assurance of one’s election. In Reformation theology, however, the doctrine of election was viewed as providing uncommon comfort to the believer. Reading Perkins’ casuistry allows us to understand that puritan divines did believe that the doctrines they espoused represented comfort, but that they also realized that, paradoxically, the more developed one’s conscience, the more likely one was to realize more fully the wretchedness of one’s sin and thus fall into despair. The casuistry of Perkins, specifically, his Cases of Conscience, are emblematic of a conscious and concerted effort on the part of Elizabethan divines in the 1590s both to preempt and treat a specific malady, despair, among the godly.