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Then build a replication architecture and a plan for downtime-free upgrades, and a plan for smooth high availability primary pairs using shared disks (using DRBD with great success).

Get in some nice MSA arrays from HP, spread load over spindles.

Get more memory, keep working set in memory, get rid of disk reads.

Learn that MySQL has a global InnoDB Buffer Pool lock, engage with my MySQL colleagues and ask for a version of MySQL with per-page locks.

Great success, and with 5.0.36 it is GA.