The specification of target reliability levels and risk acceptance criteria is one of the key issues of design and reliability assessment of existing railway structures including bridges, tunnels, or secondary structures such as noise barriers. Target reliability levels obtained by the optimization of the total cost, related to a required working life of the structure, are critically compared with human safety criteria based on group risks, intended to avoid accidents with a large number of fatalities. Practical applications of the theoretical principles are demonstrated by the examples of a railway bridge, railway tunnel, and road bridge over an important railway line. The examples illustrate on how probabilistic reliability analysis and risk optimization can support decisions about alternative strategies to achieve the optimal designs complying with the requirements on human safety. The contribution reveals that target reliability levels for civil engineering structures recommended in various normative documents are inconsistent in terms of the values and the criteria according to which the appropriate values are to be specified. The optimal target reliabilities from economic point of view primarily depend on failure consequences and costs of safety measures.