I can't speak for all the options, but Blueprint has for quite some time now had a "semantic" option where a Ruby script generates the appropriate CSS based on

I can't speak for all the options, but Blueprint has for quite some time now had a "semantic" option where a Ruby script generates the appropriate CSS based on your input. Using that you can still think of things in a logical grid format rather than pure CSS (i.e. 3 columns wide, rather than 80px), but keep your HTML clean. See the "semantic_classes" option: http://joshuaclayton.me/blueprints_compress_a_walkthrough.html http://joshuaclayton.me/blueprints_compress_a_walkthrough.ht... Not to mention if you use Compass you can do the same thing with their Blueprint mixins: http://compass-style.org/reference/blueprint/grid/ http://compass-style.org/reference/blueprint/grid/ Or if you use Less: https://github.com/omnifroodle/blueprint.less https://github.com/omnifroodle/blueprint.less