This paper reviews the key aspects associated with maintenance and safety of deteriorating infrastructure systems from a life-cycle perspective. The main conceptual aspects related to probabilistic optimization of maintenance and rehabilitation of structural systems are discussed. These aspects include life-cycle risk and sustainability assessment, risk-informed and utility-based decision making, and multi-objective optimization of interventions. In general, sustainability assessment is performed by quantifying economic, social, and environmental impacts associated with infrastructure management activities. This keynote paper also reviews various methods for determining optimum life-cycle maintenance, repair, and rehabilitation types and times, as well as the impact of such activities on the total life-cycle cost. The role of probabilistic performance indicators including reliability and risk, the sustainability assessment of deteriorating infrastructure systems, and risk-and utility-informed decision making are highlighted herein.