Since support for Lightbox2 was recently added, I tried to use it with the SWFObject API module enabled but was unsuccessful when using a YouTube video. I get the "Sorry, you need to install flash to see this content" error message within the lightbox2 iframe. The bug seem to be identical to this problem (#370909) which someone encountered using Thickbox.

If I disable the SWFObject API module, the link from the thumbnail to the video using Thickbox2 works fine.