Built to scale, or worry later?

Have a look into how WordPress.com do it – they released all the software they use under open licensing, and it’ll let you scale up in future as you need it – far as I know, DB replication is pretty easy to build in. If in doubt, email Matt (ma.tt) – the WP team are super-friendly and will point you in the right direction.

Alternatively, have a look at wpmudev.org – it isn’t free, but it looks like you have a decent budget for what you’re doing anyway – they have DB replication stuff for WP Multisite.

On the whole though, WordPress is pretty robust, especially with caching, so until you reach the top end of utilisation of your current box, I wouldn’t bother.

EDIT: in hindsight, this doesn’t fully answer your question. Keep a close eye on your load levels, that’ll tell you when it’s time to move up. The rest of this ^ is probably information you already know.

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