InnoDB

If you haven't already heard, Drupal 7 will default to using the InnoDB storage engine instead of MyISAM for MySQL (though a MyISAM database will continue to work just fine in Drupal 7). This is fairly substantial change within Drupal core, and as the thread in the issue queue I linked to shows, there were a lot of questions and apprehension about it. However...

...we are going to just skip over a lot of that apprehension and get down to point of this article - there's no good reason not to hop right into using InnoDB today on your Drupal 5 or Drupal 6 site. The rewards are; a possibly significant improvement in performance, a definite improvement in scalability (most highly trafficked Drupal sites have been using InnoDB for some time now because of this), and you'll start getting used to working with what will be more and more common in your Drupal-life, InnoDB.

My experience
I came to the conclusion about how great InnoDB is after researching the experiences of others, and after converting a large Pressflow-driven Drupal 5 site from InnoDB vs MyISAM. This change resulted in a 14% increased throughput during load tests performed in JMeter. That's a very substantial increase, and while everyone's mileage will vary based on their own site, server, and any number of variables it's clear enough to me that there's nothing to be afraid of as far as InnoDB goes (quite the contrary).

Converting your database to InnoDB
Before you go any further backup your database before doing any steps below. If you 'splode your database for any reason, you'll need it.