Safety in Cambodia is a major concern for travelers. This exotic destination has had some violent history, notably under the Khmer Rouge regime, brining some fear to travelers. Fortunately, the Khmer Rouge regime has long since vanished and is no longer a concern.
Siem Reap is probably the safest destination in Cambodia. It has become a tourist hotspot and caters accordingly.
Before even considering the issues you face, entry-requirements must first be understood. A passport is required of all nationals coming through Cambodia. Unlike many destinations however, a tourist Visa is also required. But also unlike most destinations, a tourist Visa can be obtained upon arrival, at the airport. They can even be downloaded online.
Food safety of course is an issue. Tap water is not safe in Cambodia and bottled water should be used at all times. Along these lines, make sure to eat thoroughly cooked foods.
Traffic can be quite crazy in the city; if you are concerned, steer clear of motorbike rentals! Taking a taxi or bus is your best bet.
Many tourists are concerned with the landmine issue. This is not a threat in Siem Reap; it is mainly only a problem along Cambodia's border.

