As a web developer, a number of the projects I work on fall under government umbrellas and hence are subject to 508 Accessibility laws, and sometimes W3C accessibility guideline
Progressive enhancement is certainly one route but unobtrusiveness is not the be all and end all of JavaScript accessibility as screen readers tend to use browsers as a basis for their work. Since those browsers support JavaScript, scripts on your page will still run. This is a particular problem with AJAX as clicking on one part of the page could change another part of the page that the screen reader isn't aware of.
As AJAX matures, however, methods of making it accessible are emerging. Look into the WAI-ARIA for modern methods of making AJAX accessible, and Google's AxsJAX for a good way of implementing it.