Orienting oneself in space requires establishing a correspondence between various spatial frames of reference (SFR) in which the same information about the environment can be encoded in different ways and formats. In this encoding process, one key point is the alignment of the SFRs, which may require additional operations such as a mental or real rotation. Three experiments were conducted to investigate the process of spatial orientation under aligned and misaligned conditions. Subjects were shown animated sequences of decision points perceived along a route (Experiments 1 and 2) or verbal route instructions (Experiment 3) to which they had to attribute a path on a map. The results showed that when the orientations of the map and the route were different (misalignment) both total time and errors increased. The route length (Experiment 1), and the need to reverse the direction of the path (reverse response condition in Experiments 2 and 3) also led to a decline in performance. In Experiment 3, the map-rotation strategy was found to be pertinent for solving misaligned spatial problems.