The major roads are pretty easy. Everyone knows to look both ways and proceed with caution. Most people will wait for an intersection before daring to leave the safety of the sidewalk; however, since there is no jay walking law here you may occasionally find that brave soul who throws caution to the wind and crosses in the middle of the street. My wife and I have been known to do this as well, especially on a hot day and the other side of the street beckons us with its shade. Keep in mind that when you do cross, be it at an intersection or the middle of the street, to keep an eye out for two things: motorcycles moving up between the lanes and that overzealous driver who speeds past everyone in the oncoming traffic's lane to make the green light.
Somewhat trickier are the smaller roads (two lanes or fewer) since they might be two-ways or one-ways. The signs marking these streets' directions are generally small and difficult to find, if they exist at all. This makes knowing which way to look especially tricky. Furthermore, since these smaller roads tend to be found mostly in residential areas (downtown being the big exception), people frequently cross them whenever and wherever they please. The best way to know which direction the traffic flows on these streets is to memorize it. You could look at which way the parked cars face, but that can be misleading since cars will park whichever way suits their fancy at the time. (Those of you who live in Texas know what I'm taking about.) Another seemingly smart thing to do is see which way the cars are heading and deducing from there where to look before crossing. But again, I urge you to exercise caution when doing this. Cars are known to ignore the signs--and sometimes other cars traveling in the opposite direction--to go down a one-way street so they do not have to travel around the block. It can be quite surprising to see a car whiz past you going in the wrong direction down a street that you know is a one-way.
As you may have noticed, motorcycles have no problem driving between lanes to get farther ahead. They also have one other trick they employ when they just don't want to use the streets. They drive on the sidewalk. That's right, if traffic is bad or the road just doesn't hold that magical appeal anymore the motorcyclist will opt for the sidewalk. And you better watch out. It doesn't matter if you were there first or even the trivial fact that sidewalks are made for walking, if Mr. Motorcycle wants to drive down it you are the one who's moving. To avoid this, maybe you should cross the street...
Looking both ways before crossing the street is not only sage advice passed on from mother to child; in Asunción it's a survival technique.