OK, at least they're enabled :-) I'm not a DBA, but have hit IO issues with my MYISAM/MYSQL database many times myself.
1) Have you run Mysqltuner? If not,
wget http://mysqltuner.com/mysqltuner.pl
chmod to executable
and execute it. I find it rather helpful.
2) Are you indexing every field that is part of any WHERE statement (at least for the big tables)?
3) Have you run EXPLAIN on the original query? (Suggested by someone else in this thread, and a critical question.)
4) Is the slow_query_log enabled, and are you sure about which query is causing the slowdown?
5) Have you tried tools like MySQL Administrator, which lets you monitor connections, threads, keys, queries, etc, in realtime?