First off, let me define relationship. When people talk about relationships between people most often they refer to meaningful relationships between two people. Here, I refer to a relationship as what exists between any two people - this can be familiar, romantic, platonic, professional disinterest, dislike, or strangers.

With all relationships, there are boundaries that exist. These boundaries may be of the type of "I don't feel comfortable stepping over this line" or "I don't feel comfortable when other people step over this line". These lines are often the same, but not always.

A demonstration of one of these boundaries is that of kissing.

You may be comfortable with your mother giving you a kiss on the cheek in public.
However
You may not be comfortable with giving your mother a kiss on the cheek.
Furthermore
You are not comfortable with a stranger giving you a kiss on the cheek.

Difficulty and confusion arises when two people are uncertain of the boundaries that exist. This most often occurs when the two people are familiar with each other on some level but not well acquainted with each other. Most often, this is the case with a friend of a friend or co-worker in a non-work environment.

This comes as a surprise to some, however the boundaries in most other areas are already well defined over time or by society. There is a distance that society dictates that we keep around us in the presence of strangers. Likewise, there are certain topics of conversation that are rather well defined and non-threatening. With disinterest and dislike the personal space becomes even larger and topics of conversations even more restricted.

With romantic relationships, communication is especially important (not that it is not important in other relationships). Here, the boundaries become fuzzier (and in some case more more clear) with the aid of communication. Here, occasional steps over boundaries may be allowed as people grow closer and things become more relaxed.

As mentioned above, the greatest difficulty occurs when two people are familiar to the point which they might accidently cross a boundary that one or the other is unaware of. When this happens the best thing to do is to apologize, identify the boundary and avoid crossing it again. Realize that although that mapping our own boundaries on other people (don't do to others what you don't want done to you - AKA The Golden Rule) is a good place to start, each person is unique with his or her own boundaries.