A few weeks back, I was working on a customer issue wherein they were observing database performance that dropped through the floor (to the point of an outage) roughly every 4 weeks or so. Nothing special about the environment, the hardware, or the queries; really, the majority of the database was a single table with an auto-incrementing integer PK and a secondary UNIQUE KEY.
The queries being run against this table were almost exclusively INSERT … ON DUPLICATE KEY UPDATE (INSERT ODKU), with the columns from the INSERT part of the statement corresponding to the columns in the secondary index, and they were coming in at a rate of approximately 1500 to 2000 per second, sustained, 24h per day. The mathematically-astute among you may already be able to see where this is going.
For purposes of discussion, we can use the following table to illustrate the situation: