1. Your friend is selfish.
Perhaps your BFF is going through a particularly hard time and really needs an ear, or has an ongoing problem that she feels comfortable enough talking to you about - it's perfectly okay to let her do most of the talking. However, there's a big difference between lending a friend an ear and having a friend use you as her personal therapist. If you find that all of your conversations are one-sided, or that your friend doesn't seem to care very much about problems occurring in your life, it might be time to stage a friendship intervention. If your friend isn't particularly responsive towards your concerns, then it might be time to take a step back.
2. Your friend is a negative influence.
Remember all of those "Very Special Episodes" of '90s sitcoms that featured a "bad girl" encouraging her more uptight friend to smoke, drink, or cause general debauchery? It's not quite so easy to spot those girls in real life (i.e., they don't always wear leather jackets) but if you find that your friend is constantly pushing you to do things you're not comfortable with, it might be time to cut her loose. Run and don't look back if your friend is encouraging you to match her particularly destructive habits, like dangerous drug use or disordered eating.
3. Your friend is highly competitive.
Some people are born with a competitive streak, but that's the kind of thing best left on the soccer field. If you find that your BFF is constantly trying to one-up you in every aspect of your life and seems to be keeping score of everything she does better than you, you might want to leave this frenemy in the dust.
4. Your friend has no problem putting you down.
Inside jokes and light teasing are one thing, but if your friend's comments feel more like an insult than a joke, don't put up with it. If your friend really has no idea how badly his or her words hurt you - after you say something about it, then they'll stop with the bashing immediately. If not, they suck... and are SO not worth continuing a friendship with.
5. Your friend has betrayed you in a major way - and didn't learn from it.
I'm all about giving people second (and sometimes even third) chances, but if your friend has hurt you in a serious way and doesn't show any signs of changing even after the apology, it's time to walk away. If your friend won't stop trash talking you or flirting with the guy you're dating even after you've confronted her about it, she's not a real friend. Bye, Felicia - and don't come back.