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Nope. Screen readers have been able to handle javascript-generated content for years. According to WebAIM's most recent screen-reader survey, 98.4% of screen reader users have javascript enabled: http://webaim.org/projects/screenreadersurvey3/#javascript

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Crawlers, less so. The major search engines are getting smarter about it, but for now, you still need some kind of HTML output from the server if you really want to be indexed properly.

It doesn't rule out a pure client-side app at all, but you do have some extra work involved to output HTML from the server. Which is why NodeJS will ride on the coat-tails of this approach; less redundancy.

Hah! "The major search engines" - you mean Google, right? ;)

How effective is Javascript with screen readers, though? It's been a while since I played with a screen reader (late 2009 or so), but when I did even really simple things like a pop-up div confused it. It didn't inform the user that something new was being rendered or anything.

Surprisingly effective. A colleague of mine published some techniques to add consistency to Javascript events across screen readers: https://github.com/ryanfitzer/Accessibility

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