Here are the big indicators that it’s time to move on.
You’re stagnant. If you aren’t going anywhere, and haven’t for a significant amount of time. Be careful that you’re not just being impatient—we can’t all make Vice President before we’re 30. But if you were promised mobility and three years later you’re still answering phones and fetching coffee, it might be time to seek another opportunity. (First make sure you’ve done everything you can to get ahead—you’ve learned everything about your industry, shown initiative on new projects, and volunteered for extra assignments.)
Your job is toxic. If your job makes you so unhappy that it’s doing serious mental harm, it’s time to go. It could be a bullying boss, unmanageable workload, or a demeaning work environment, but if you find yourself depressed, experiencing stress headaches or illness, or taking drugs or alcohol just to get through the day, please leave your job. (Again, self-assess to make sure it’s truly the job that is causing the stress. Lots of people don’t care for their jobs, but there is a big difference between not wanting to go every day, and considering self-harm to get out of it.)
Work interferes with your quality of life. If working late every day means you miss every one of your kid’s swim meets, it may be time to prioritize. If you moved to the Northwest for the great rock-climbing opportunities, but the only time you spend outdoors is when you walk from the front door to the car, a different job may be for you.
You get a better offer. If the job is for more money, increased responsibility, or takes you a direction you’d been hoping to go, follow it. You might even find that your current company matches their offer, just to keep you on board.
You’re ready to change careers. You’ve decided you’ve gone as far as you want to in molecular engineering, and you’re ready to be a firefighter. Go for it.
Careful! The grass out there isn’t always greener. The problem with the unknown is that you could find yourself in a situation just like the one you left, or worse. The devil you know if often better than the devil you don’t know, so keep that in mind while you look for a new job. And unless you’re independently wealthy, try to have a new job lined up before you quit the first one.