This paper presents the RISK-UE methodology for the seismic risk assessment of utility systems (potable water, waste-water, gas system, telecommunication, electric power) and transportation infrastructures (port, airport, road and railway system). The proposed methodology provides a uniform basis for the reduction of the consequences of lifeline damages in urban areas and an efficient mitigation strategy and prioritization policies for pre-earthquake and post earthquake actions. A detailed inventory for every element at risk together with a reliable seismic hazard assessment, appropriate selection of fragility models, estimation of the “global value” and economical impact of lifeline damages and losses are the main steps of the proposed methodology. The consideration of European distinctive features of lifelines and utility systems in the construction of seismic scenarios and the proposition of fragility curves are among the basic aims of the proposed methodology. Different modules of the methodology were applied in seven pilot cities (Thessaloniki, Catania, Nice, Bucharest, Sofia, Barcelona, Bitola). We present herein few representative examples (case studies) in order to illustrate the methodology and to prove its efficiency.