Much of the earliest research on personality pathology was observational and descriptive in nature, drawing heavily on subjective self-reports, however, the last 20 years have seen a surge of interest in laboratory-based studies. Laboratory research offers a number of benefits for researchers interested in personality disorders and personality pathology including the opportunities to use objective performance-based and behavioral measures, reveal the neuropsychological and biobehavioral processes that may help shape the experience and behavior of individuals with personality disorders, and create experimental designs that allow researchers to systematically explore the effect of context on emotional, behavioral and cognitive responding. Along with these benefits, laboratory research on personality disorders has its share of methodological and interpretive challenges and raise several key questions, including (a) How should we interpret findings that diverge from theory-driven predictions? (b) How do we reconcile discrepant results from subjective and performance-based assessments? and (c) Are these discrepancies due to methodological artifact, a hallmark of the disorder, or cause for theoretical reconsideration? The goal of this article is to review studies aimed at answering a key research question in the domains of borderline personality disorder, psychopathy, and schizotypy. Our review highlights significant progress in laboratory research on personality disorders, and identifies challenges that must be addressed to capitalize on the promise of laboratory methods. It is our hope that future experimental work proceeds with an eye toward theoretical coherence, methodological rigor, ecological validity, and clinical utility.