Focusing on collusive behavior, this chapter outlines the complexity associated with both ex ante designing of antitrust compliance programs and ex post assessment of their impact. Following an interdisciplinary review of relevant literature, the chapter provides a structured cost–benefit approach to compliance and challenges the idea that compliance cannot be rationalized. We recognize that measurement of compliance programs may be particularly difficult in light of the importance of less-tangible factors such as corporate culture. Yet, the chapter proposes that a principled approach to compliance would considerably support the work of practitioners. Future research should concentrate on studying the interaction effects of compliance mechanisms and corporate culture. Such large-scale empirical studies on individual and firm-specific factors of compliance might be promoted and coordinated by competition authorities.