Many large web sites use reverse proxy servers in front end. For example flicker use squid in reverse proxy mode, wordpress use varnish in front end.
Varnish was written from the ground up to be a high performance caching reverse proxy. Squid is a forward proxy that can be configured as a reverse proxy. Besides – Squid is rather old and designed like computer programs where supposed to be designed in 1980.
http://varnish.projects.linpro.no/
2 cache servers (1 in each datacenter). These servers are running Varnish. They cache requested images for a period of 10 minutes, so frequently requested images are not repeatedly requested from the application servers. We are seeing about a 65% cache hit rate and about 1000 requests/second at peak times, although as adoption of the service increases, we expect this number to go up significantly. A single server running Varnish can serve many thousands of requests/sec. The amount of data we are caching is small enough to fit in RAM, so disk I/O is not currently an issue.
Read about wordpress.com scaling at
http://barry.wordpress.com/2007/10/26/making-gravatar-fast-again/
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