The post-translational modifier, ubiquitin, controls many aspects of eukaryotic cell biology, including key aspects of both innate and adaptive immune signaling. Remarkably, despite having no such system of their own, viruses and bacteria have evolved strategies to manipulate ubiquitin signaling of the host cell to support infection. A common strategy to both pathogens is the adaptation of specialized proteases, termed deubiquitinases, that can remove host ubiquitin signals. Though the current body of work suggests that the removal of host ubiquitin signals is a common strategy for virulence, the identification of novel deubiquitinases has been impeded by significant differences in primary sequences that likely indicate an evolutionary convergence in function. Since development of deubiquitinases typically derive from structural mimicry, this allows for diversity in the primary sequences that may make motif searching for deubiquitinases difficult.