Basically, a commercial airliner on route from Australia to Lost Angeles crashes on an island somewhere in the south Pacific. There were many survivors split between the front end and tail end of the plane which crashed in 2 different parts of the island.
There were inhabitants already on the island (called "The Others") but they are not native to the island and so far, we've been told that they arrived themselves sometime in the '60's.
The show mainly focuses on the survivors and their interactions with The Others and the show has taken on a "6 degrees of separation" quality. Almost all of the characters are tied to each other through past experiences and other people in their lives. Some of them become aware of this and others still are not aware as only the (TV) audience knows their combined histories.
This interconnectivity is further enforced when it is revealed that The Others were running experiments on the island because the island itself has a weird energy on it that allows for the most amazing things from time travel to resurrections from the dead. There are people aware of this power, (outside of the island) there is a struggle to control it and these passengers landed right in the middle of their struggle. We've been led to believe that the survivors fates were tied to the island long before they boarded the plane that stranded them the but only time will tell if this is truth or manipulation.
If this intrigues you, I suggest renting the series from season 1; DO NOT START IN THE MIDDLE. Netfirms or Blockbuster online will make this really cheap for you.
As others have suggested, unless I write a book, I can't tell you everything but it really is a good show. The writers (and the show) got a little dry around the writer's strike a few years ago but it's gotten better. You will need patience though, it reminds me of the X-Files, plenty of questions, not a lot of answers...yet!