This may sound overly rational or perhaps even cold, but I think that all relationships are fundamentally about exchanges of value. Ideally, each person derives more value than the expend from engaging in a relationship. When I say value, I'm talking about psycho-emotional value; do you enjoy engaging in this relationship, does this relationship make you feel a way about your self that you want to feel, etc. In my mind, it is healthy for relationships to end when one or all of the participants are losing net value. Now, this being said, I think that many people would read this as advising against sticking around through tough patches etc., and that is not my intention. Putting in the work to develop your relationships, though often difficult and unpleasant, often provides positive value in the long term, as you strengthen your relationships and are able to provide and derive more value from each other.
However, if you can look at a given relationship and realize "I don't think I've been getting enough value from this relationship to make it worth what I'm spending in time, emotions, energy, etc., and I don't see how that is going to change any time soon" it may be time to move on. Remember too that this does not need to be a permanent end. Two people can realize that they're not at points in their lives right now where they're able to help each other, and later in their lives come together again now that they can.