I am currently using information_schema.TABLES to calculate the total disk space usage grouped by the database name, but it is running terribly slowly. On servers with hundreds of databases, it can take minutes to calculate.

What is the quickest method of calculating disk space usage by database? Should I just be looking at the filesystem? Is there a method for speeding up information_schema?

There are 3 scenarios.  


If you are using MyISAM, it is easiest to just look at the filesystem and use du -sh /var/lib/mysql/database.
If you are using InnoDB with innodb_file_per_table set, then you can get an approximate answer using du -sh.  It is approximate because there is still some data stored in the ibdata1 file, so you will be a little on the low side.  This technique also works with mixed MyISAM/InnoDB (innodb_file_per_table) databases.
If you are using InnoDB without innodb_file_per_table set, then you will need to look at INFORMATION_SCHEMA.


In any of the cases above, you can run the following query to get the information that you are looking for.  

mysql> select table_schema, sum((data_length+index_length)/1024/1024) AS MB from information_schema.tables group by 1;
+--------------------+-----------------+
| table_schema       | MB              |
+--------------------+-----------------+
| prod               | 298025.72448921 |
| information_schema |      0.00781248 |
| maatkit            |     70.77330779 |
| mysql              |      0.66873168 |
| test               |   4752.31449127 |
+--------------------+-----------------+
5 rows in set (0.01 sec)


If you have a very large number of tables, it can be slow, as you have already discovered.
