We run a forum with some 2 million posts and I've noticed that if left untouched the overhead in the mySQL (as listed in phpMyAdmin) can get quite large (hundreds of megabytes).

I'm wondering if scheduling a normal mysqlcheck to optimize the tables is good practice? Any reason not to do it, say, once a week at an off-peak hour?

There was a time over the summer where our site was constantly crashing because mysql was using up all resources. That's when I noticed the huge amount of overhead and optimized the database and haven't had any problems since then with stability. I figured if that was helping alleviate the issues, I should just setup a cron to automatically do this.