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Generally, all of Germany does not have a big crime problem. Cities are normally safe and even at night it is possible to walk home without the need to be afraid. Murder out of the blue is very seldom, if existent at all. Frankfurt is no exception to this general rule. Still, like in any western city, it is a good idea to watch your back at night when you are alone on the street. Frankfurt is Germany's crime capital by a small margin, so there is some reason to be cautious about strangers approaching you (especially at night). For West European and American travellers the best advice is to behave as they would do in their own cities.
Things most likely to happen are theft and robbery, especially in areas like the red-light district around Hauptbahnhof (drug-related crime might be most likely here) and in the area around Konstablerwache. Travellers shouldn't be too credulous about apparently helpful strangers - fraud does happen every now and then. Remote suburbs like Bonames or Rödelheim might also have minor American-style gangs who simply like to show that they are stronger than you. Still, there are no "slums" or "banlieues", so actually there is no area that must be specifically avoided.
Politically motivated crime and xenophobia is not common in the area around Frankfurt as the city itself is quite cosmopolitan with 22.5% of its population being immigrants.