Over the past year I've had to come up to speed on this question for a project my company's working on, and I've found these resources extremely helpful: Todd Hoff's highscalability.com; Scalable Internet Architectures, by Theo Schlossnagle; and Building Scalable Web Sites, by Cal Henderson. Highscalability.com in particular will point you to many good presenations, tutorials, books, and papers, and is a great place to start. All of the advice is practical, and based on experience at sites like Flickr, Twitter, and Google.
BTW, scalability is not performance. A perfectly scalable system is one that has a fixed marginal cost to add additional users or capacity.
Building Scalable Web sites has a nice section on handling email. It's written by a Flickr developer.
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I've worked on a few sites that get millions/hits/month backed by PHP & MySQL. Here are some basics:
I'd recommend reading Building Scalable Websites, it was written by one of the Flickr engineers and is a great reference.
Check out my blog post about scalability too, it has a lot of links to presentations about scaling with multiple languages and platforms:
EDIT Interesting annecdote... Cal Henderson is the author of "Building Scalable Websites" http://www.amazon.com/gp/product/0596102356 and has worked in "the trenches" as the lead engineer of FLICKR and developer at B3TA.
Apparently his newest company http://tinyspeck.com/ is using node.js for their game engine.
Assuming he's planning on scaling to a reasonable size, that seems to be a pretty resounding endorsement that there's at least something going for it. I mean ... that guy's got a bit of experience in working at scale.
- JOS software reading list 
- JOS management reading list 
There are gaps in these lists but pretty much cover the best for both programmers & business - types. But the lists needs updating as I note pg's 'Painters & Hackers' is not listed nor is Cal Hendersons 'Building Scalable Websites' .
 Joel On Software 'Book Review, reading list'
 Joel On Software, 'Management reading list'
 Cal Henderson, 'Building Scalable Web Sites, 978-0596102357':