Probably not too badly, actually. Jews run into this fairly often, and I have yet to hear of an employer firing an Orthodox Jew because he wouldn't work on Shabbos. IANAL, but I suspect the EEOC would come down on such an employer like a ton of bricks.
RandFan wasn't talking about religious accomodation, but even if he had been, it would depend on whether or not it would be considered an "undue hardship" for the employer to accommodate the employee. In most cases, if a position requires an employee to work on Saturdays, an employer may choose not to hire an Orthodox Jew who doesn't work on Saturdays for religious reasons.
BTW, the EEOC Compliance Manual is online here:
http://www.eeoc.gov/policy/docs/religion.html
Title VII requires an employer, once on notice, to reasonably accommodate an employee whose sincerely held religious belief, practice, or observance conflicts with a work requirement, unless providing the accommodation would create an undue hardship.[116] However, the Title VII “undue hardship” defense is defined very differently than the “undue hardship” defense for disability accommodation under the Americans with Disabilities Act (ADA). Under Title VII, the undue hardship defense to providing religious accommodation requires a showing that the proposed accommodation in a particular case poses a “more than de minimis” cost or burden, which is a far lower standard for an employer to meet than undue hardship under the ADA, which is defined in that statute as “significant difficulty or expense.”[117]
-Bri
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