The short answer is yes. The long answer depends on how you define luxury. If your quest is for a few nights at a Banyan Tree resort in Asia, the popular travel websites are probably not your best bet. In fact, you should probably prepare yourself to pay list price. If you're happy at one of the more mainstream luxury brands, then there is hope for the discount travel sites.
Unfortunately, it usually means shopping around. I am personally leery of priceline.com's bidding system, only because I like to know with some certainty where I am staying (and my definition of 5-star and theirs doesn't always align). Beyond that, I would say the best results I've seen come when booking a plane flight and hotel stay together. The only time I've succeed with any of the sites is at cheaptickets.com.
Whatever you find on the mainstream sites, I would encourage you to check out the website of the hotel brand before buying. That tends to be where I find the best deals. I'm not sure if the big brands are trying to maintain their luxury cache by avoiding the discount sites, or they just don't want to pay a commission to the sites. Either way, I tend to have better success with high-end hotels, purchasing direct from the hotels.
