South America us huge, and full of interesting places to explore. Distances between destinations aren't short, there are no trains to speak of, and flights aren't exactly budget, so you'll probably spend a fair bit of time on buses. We've travelled a fair bit by bus in Chle and Peru, and we've picked up a few ideas that could help to smooth your journey.
For journeys of less than six hours, your best bet is to travel by day and enjoy the scenery (at least in the south of Chile, in the north it's quite repetitive). But for longer journeys, save your days for sight-seeing and travel by night.
The buses are generally safe and comfortable, and you can increase your comfort by paying more for a better seat. The names vary from company to company, but generally there are four classes of seats on night buses.
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