For one thing, graphics and GUIs are add-ons to lisp, rather than built-in like smalltalk.

Also, most lispers seem to be very adept at Emacs, which is very powerful, but hard to learn well, and very keyboard-intensive.

I've had daydreams about creating a smalltalk-style environment for lisp, either by implementing a lisp in smalltalk, or by recreating a lisp version of the smalltalk libraries and frameworks. Sounds like a LOT of work, but what fun!