So there are a couple of clips up previewing next week's episode. I had postulated that the title might reference Jack "substituting" for Sayid, but now I'm not so sure. The obvious connection to the title is John Locke being "the substitute" for Christian Shephard's body on the return trip to the island. From the clips below it is clear that the upcoming episode is Locke/Smoky-centric (color me excited!). Of course it's entirely possible that the writers have chosen this title to have a double meaning and that both interpretations (or neither) are correct. Anyway, here are the clips.
Tell me that second clip hasn't majorly peeked your interest? "The most important question in the world"!? That really raises the stakes doesn't it? Tuesday can't come soon enough.