Past and recent events have proved that critical infrastructure are vulnerable to natural catastrophes, unintentional accidents and terrorist attacks. Protecting these systems is critical to avoid loss of life and to guard against economical upheaval. A systematic approach to plan security investments is paramount to guarantee that limited protection resources are utilized in the most effcient manner. This thesis provides a detailed review of the optimization models that have been introduced in the past to identify vulnerabilities and protection plans for critical infrastructure. The main objective of this thesis is to study new and more realistic models to protect transportation infrastructure such as railway and road systems against man made and natural disruptions. Solution algorithms are devised to effciently solve the complex formulations proposed. Finally, several illustrative case studies are analysed to demonstrate how solving these models can be used to support effcient protection decisions.