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I've used eAccelerator with success for busy sites - the one downside to this cache system is that its directory apparently needs to be deleted of all cached files before restarting Apache. This is one step that is easily forgotten without a special script to do it automatically and can be cumbersome.
The first thing that you would want to do before adding any cache system is to see if/how you can optimize your database queries. Use MySQL's EXPLAIN function to see how well a query is performing:
Usually, adding indexes on fields that are queried often helps in the overall performance of the MySQL-based web site, but the queries themselves may be able to be rewritten for better performance.
Hope this helps,
[edited by: coopster at 9:32 pm (utc) on July 28, 2007]
[edit reason] changed link to authoritative domain [/edit]