To get Simple Lightbox working with Google Chrome 36.x I added handler.image.js to the Exclude scripts list.
Simple Lightbox works fine with the latest versions of IE, Firefox, Safari, etc. but without an exclusion for handler.image.js it won't work with Chrome, rather the image opened as if Simple Lightbox were disabled.
I have a jQuery-based theme by WooThemes and the following options enabled in Autoptimize:
Look for scripts only in <head>? - checked
Exclude scripts from Autoptimize: handler.image.js
I found the handler.image.js solution by looking through the Simple Lightbox plugin files and testing. The image handler appeared to be a good candidate.
CSS Options - all disabled for compatibility with IE8. I'll probably drop support for older IE versions soon. BrowserStack is an excellent service to check for browser issues.