When a print job is finished correctly the folds are unlikely to attract attention, but poorly planned folds can result in a distracting flaw: cracking of the paper surface, which is especially noticeable when ink coverage crosses the fold.
The best prevention is to score the paper before folding, which embosses a crease into the paper fibers and forms a hinge.
Usually it makes sense to plan projects so that the folds run parallel to the grain of the paper, which makes them crisper and less likely to crack. However, if your print job will be handled a lot or be in service for a long time, consider orienting the paper cross-grain to the folds. Although the folds won’t be as tight, they will be more resilient.
Paper selection is also important. Generally, the glossier and heavier the paper, the more likely cracking becomes.
If your printing project calls for a lighter weight of paper with high gloss, it will be too thin to carry a score. Minimize visibility of cracking by avoiding dark or heavy coverage across folds on such projects.