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Pressflow might be your answer.
Pressflow is designed for large-scale high-performance implementations of Drupal. It abandons support for out-dated versions of PHP and required MySQL version 5.x. It is also designed to take advantage of more advanced caching systems (e.g. memcached and APC) which are typically only available in dedicated hosting environments.
If you are using a typical “shared” hosting account (e.g. not dedicated or VPS), you will have a hard time taking advantage of much of what Pressflow has to offer. Similarly, if your traffic is modest, you may find it easier to stick with vanilla Drupal.
However, if you have a VPS or dedicated hosting, have 10s of thousands (to 10s of millions) of pageviews, are interested in using advanced caching systems like Varnish, and are concerned with growing traffic or traffic spikes, Pressflow is designed for you.