Background
We use MySQL for storing all of the data in FriendFeed. Our database has grown a lot as our user base has grown. We now store over 250 million entries and a bunch of other data, from comments and "likes" to friend lists.
As our database has grown, we have tried to iteratively deal with the scaling issues that come with rapid growth. We did the typical things, like using read slaves and memcache to increase read throughput and sharding our database to improve write throughput. However, as we grew, scaling our existing features to accomodate more traffic turned out to be much less of an issue than adding new features.
In particular, making schema changes or adding indexes to a database with more than 10 - 20 million rows completely locks the database for hours at a time. Removing old indexes takes just as much time, and not removing them hurts performance because the database will continue to read and write to those unused blocks on every INSERT, pushing important blocks out of memory. There are complex operational procedures you can do to circumvent these problems (like setting up the new index on a slave, and then swapping the slave and the master), but those procedures are so error prone and heavyweight, they implicitly discouraged our adding features that would require schema/index changes. Since our databases are all heavily sharded, the relational features of MySQL like JOIN have never been useful to us, so we decided to look outside of the realm of RDBMS.
