A manager told me that she was frustrated with her place of employment because a new manager had been promoted to the position superior to hers.  He was making changes that she was uncomfortable with and was considering leaving the company.  Now I'm totally in favor of changing jobs to enhance your career or your pocketbook, but here's some of the thought process I'd go through before jumping ship.
First, be clear about what is motivating you.  Is it the desire to “get away” from where you are or the desire to “move toward” a better opportunity?  You can answer, “both,” but if you reflect deeply, it’s usually a little more one than the other.

Moving to a new place of employment doesn’t necessarily guarantee “getting away” from organizational change or a heavy workload imposed by upper management.  When you’ve worked at one place for a long period of time, you may have the tendency to assume that things must be better elsewhere.  It’s my opinion that this perspective arises as the result of your intimate knowledge of the problems in your current position versus the lack of knowledge about the problems at any new organization.  Change occurs everywhere and it most often comes without warning.  Expect it where you are now or at the organization you move to. 

If you are trying to get away from your current workload, and this is enough to cause you to seek other employment, make sure you understand the true challenges and issues that will face you in your new position.  Ask probing questions.  Know what you’re getting into.  Starting over with a new organization may be more taxing on you then dealing with the situation you’re already familiar with.

Now let’s look at it from the other perspective.  Moving toward a new position may give you the opportunity to freshen your outlook on your career (re-invigorate you) and allow you to make your next promotion.  Let's assume you want to become a Director in your current organization but that position is blocked.  If you feel you are qualified for the position of Director in your current organization you may be qualified to be a Director at similar organization - right now.  

Making a career move like this from your current position will require tact, diplomacy and some stealth to investigate this move without revealing your plan to your current employer.  After all, you may find that you are in the best place after all.  So be careful not to indicate to your current employer that you’re ready to leave. 

Looking for that next position is good for you and the economy.  Knowing what opportunities are out there (or not out there) can spur you on to better things or give you a sense of satisfaction knowing you are in the best position.  Knowledgeable employees keep employers on their toes which makes the economy as a whole stronger and more competitive.  Keep in mind, this search will become something akin to a part time job, but if you want to make a solid career move, it is necessary. 

Having said all that, I know job candidates who have been offered a desirable opportunity within their current company simply by saying something like this to the right person at the right time, “You know, I think I’m looking for a new challenge.  Are there other opportunities available now or are their new positions on the horizon that I might apply for?”
If you're asking yourself whether it’s time to leave take another moment to look closely at your current situation.  Take time to really understand the source of your discontent.  Write down you’re ideal working situation.  How does it match where you are now?  Make a list of what you like and dislike about your current position.  Sometimes you may find that you’re able to be happier where you are if you can make a few minor changes in your responsibilities, compensation or status.  Otherwise it can become clear that only a change to another organization will satisfy you.  Either way, your mood will improve when you begin to take action on your plan.