I was sitting in the left seat of my Cessna 340 getting set for a check ride with my friend a US Air pilot. We were going to do the usual procedures: airwork, simulated engine out and some practice approaches. But before we got started, he asked the following: if the weather is down to or close to minimums for a radius of 300 miles or so would you take-off. Good question. I wasn't sure of the answer, as the Cessna 340 could easily overfly the bad weather and get to something better. But what if all did not go as planned and an imminent landing was needed? Now under duress an instrument landing to minimums or less might be necessary with one engine running rough or out. Worse yet if we were flying a single and developed engine problems. Or what if the forecast weather beyond the 300 miles goes down and the amount of fuel becomes a problem. Remember that you are required to have enough fuel to reach an alternate and still have 45 minutes of fuel aboard. So better stop and think it through. Leave yourself an out. If you try to cut it too close you may lose and end up a statistic.
Moral: Always leave yourself an out. Don't get boxed in.