I mostly do Java server side development for a living and I have been getting into Ruby on Rails the last 4 or 5 months. That said, the Seaside web application framework is incredibly compelling. It runs either on the free Squeak Smalltalk or the commercial VisualWorks Smalltalk systems.
I don't have a secure feeling as to how far up Seaside will scale and what its stability is, but I am starting to see more commercial web portals written with it - a good sign! Even though I have been programming Smalltalk off and on (mostly off) since the mid 1980s, my Smalltalk skills are weak - I always need to use the language and environment for a while before I get back into it. So, take my analogy with a 'grain of salt': if building web apps in Java, PHP, etc., is like carving something out of rock, Seaside is like using clay. Install Squeak 3.8, follow the simple Seaside installation instructions and first tutorial, and see what I mean.