Big cities can be dangerous, car jacking in the big cities is a real and common problem. If you are driving in the big cities stick to highways as much as possible, and make sure you know exactly where you're going. You don't want to be stuck in a bad neighborhood as it can lead to real problems. With that you should also make sure your doors are always locked, and never pull over to help other, it's a common scam and can get you into a lot of trouble.
Outside of the cities there are a few problems that come up with driving in Southern Africa. The first problem comes with road conditions. Depending on the country you're visiting, sometimes the roads aren't in the best of shape. For the most part South African roads are OK, as well as the roads in Botswana. However some countries (and even some areas of South Africa and Botswana) don't have the budget to maintain roads. Because of this 4x4 trucks may be the way to go if you're traveling in certain areas.
Speaking of 4x4s, when it comes to Safaris, 4x4s are often a necessity. Unless it's marked as a safe drive for two wheel drive cars, assume a 4x4 is needed. In many cases the park rangers will not let you into the park unless you have a 4x4, however if you happen to sneak your way in, you're in for a lot of potential trouble. Having said that, even if a road is marked as two wheel drive friendly, the chances of it being a completely smooth ride are slim, and you'll want to drive with caution.
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