Since the beginning of the twenty-first century, Italy has implemented legislative measures aimed at improving the standard of detention. These measures have resulted in the construction of new facilities and the closure of old prisons. Currently, some of these facilities are still awaiting new uses. It is well known that these architectural structures have a strong identity and can have significant psychological, social, and economic impacts on future users due to their location in the urban context and large size. The proposal aims to identify critical issues that must be considered when selecting a new function for decommissioned historic prisons. This analysis allows for the evaluation of the proposed reuse in terms of conserving and enhancing both tangible and intangible values, as well as its sustainability. By examining national and international case studies formulated since the latter half of the twentieth century, the main design trends for the reuse of this challenging heritage have been identified. The results obtained from a thorough study can support the decision-making process for the restoration and reuse of other former prisons that are still awaiting new projects.