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Infrastructure systems have legacies that continue to define their priorities, goals, flexibility, and ability to make sense of their environments. These legacies may or may not align with future needs, but regardless of alignment, they may restrict viable pathways forward. Infrastructure ‘lock-in’ has not been sufficiently confronted in infrastructure systems. Lock-in can loosely be interpreted as internal and external pressures that constrain a system, and it encourages self-reinforcing feedback where the system becomes resistant to change. By acknowledging and recognizing that lock-in exists at small and large scales, perpetuated by individuals, organizations, and institutions, infrastructure managers can critically reflect upon biases, assumptions, and decision-making approaches. This article describes six distinct domains of lock-in: technological, social, economic, individual, institutional, and epistemic. Following this description, strategies for unlocking lock-in, broadly and by domain, are explored before being contextualized to infrastructure systems. Ultimately, infrastructure managers must make a decision between a locked in and faltering but familiar system or a changing and responsive but unfamiliar system, where both are, inevitably, accepting higher levels of risk than typically accustomed.