A few things about me that may or may not be important to know before reading this and offering advice:
1) My lifetime score is somewhere around 45 or 50, most of which were one-nighters
2) I mostly grew bored of one-nighters after about 30 of them and am more interested in long-term dating/hookups. 30 might seem low to some of you, but I grow bored of things easily so that's how it is.
3) Because I was a bit of late bloomer, my longest committed relationship to date was only 6 months (I'm currently 25).

There's this girl that I've known and been friends with for about 5 or 6 years. We've always had a mutual attraction and sexual tension between us, but aside from a couple of drunken make outs just never really acted on it for some reason. We recently hung out and hooked up (she initiated it), agreed that it was long overdue, and talked about starting to hang out more often and seeing if we want to get serious. We had plans for tonight, but she texted me this morning that her boss asked her to go to Massachusetts with him (4 hours away) to help close a deal so she might not make it. A little before 5 she told me they were staying overnight, officially cancelling our plans though, realistically I expectied this would be the case from the first text in the morning. This is the 2nd set of plans she has cancelled on since we hooked up and talked about seeing each other more.

I like this girl and want to believe her reasons for cancelling twice are legit, but I'm worried that I'm just being naive because we've known each other so long. I know that if I had just met this girl, I wouldn't even second guess that it was probably BS, but I've never tried to get involved with someone I've known this long before and I don't know if I should approach this differently than with a girl I don't know that well.

Has anyone here ever gotten involved with a girl they've known for a long time? In what ways, if any, should I approach a situation like this differently than a girl I've just met? What do you think of this particular series of events with the cancelled plans?

Don't complicate things. And yes, you have definitely more value in her eyes, and approach should be definitely different, given situation. Take some time, think about it. You don't have to add a necessary time-constraint here. Re-read the messages, and try to understand her intentions.

As you wrote, in first message she said, that "she might not make it!", and later just confirmed what she said earlier. Did you write any message between that time period to affect her decision? If not, you didn't make any mistakes, and she's probably have a legit reason.

Go on and analyze your last conversations, to get the feel. In situation like these, it's important to know, what to work with. You should definitely make her think, that she owes you in some way about missing/not meeting your plans. Preferably, in-direct way. Then you can mirror her, and see her reaction and figure it out.

Instead of talking about hanging-out, actually hang-out. Don't get attached a lot, these relationships are also working out much differently than with strangers.

Ok. That all makes sense. The thing here is I don't doubt that she actually had to go to Massachusetts, it just seems strange to me that a trip to Massachusetts would suddenly get sprung on her right when she got to work. Things like that are pretty much always planned in advance so it makes me think she might've known she couldn't keep the plans when we made them. I definitely didn't say anything during the the in-between texts that would have an influence, and when she told me they were staying the night I playfully asked how she was going to make it up to me. Your comment about mirroring her is definitely helpful. I realize now I definitely haven't been doing that well enough in our interactions and text convos.

Thanks a bunch for the input.

If something feels fishy, it could be fishy. Don't trust her right away. With all the information you provided, there is always a possibility that she is just playing the same game as you, trying to trigger your emotions.

Can you actually think she could be capable of doing that? You should know her background a bit, just make up your mind about her general EMOTIONS, MOTIVATION and TRAITS. From that, just form a profile, that will help you as well in strengthening the relationships.

For example, why did she mention her boss? Is he a male/female? If in case, the boss is a guy and she's interested in you, she would definitely not to mention things like "i'm going on work with other guy", "i'm staying overnight with my boss" - probably just skipping most parts involving any other man. She would say "she's going for work", "i'm staying overnight".

As to end this post, you should focus on some other things as well, the main rule is to not to let this affect or damage you in any way. But you know that already.