The search for mechanisms in personality disorders (PDs) is of growing importance, because PDs are prevalent, costly, and challenging to treat. Unfortunately, there is a dearth of compelling mechanistic research on PDs and psychopathology more broadly, due to equivocal definitions of a “mechanism” and study designs that are atheoretical and/or ill-suited for causal inferences.This chapter defines mechanisms as elements of possible causal sequence, which not only increase the probability of observed outcomes but also reveal how the outcomes occur. In addition, the authors argue that it is not always necessary to break down a mechanism to its most elemental physical parts; rather, it is important to consider how mechanisms act as complex, interacting components of a causal chain, with a focus on those that could serve as viable targets for prevention and intervention. Considering this broader definition of a “mechanism,” it is crucial that PD researchers ground their work in testable theories, such as those considering dimensional, transdiagnostic precursors to PDs. In this chapter, the authors also address various design and statistical considerations in PD mechanistic research and highlight promising developments in identifying mechanisms of PDs across multiple levels of measurement (e.g., biological, contextual, environmental) and across the lifespan.