This is one of my all time favorites. David Byrne appears as a mad man mystic channeling messages from the universe. Of course each person who experiences this will have his or her own take on what Byrne is trying to say. That is part of what gives the song and the performance its genius in my opinion. For me the song is about getting lost in the day to day that kills our time and fills our lives(or vice versa) and not being fully aware of the life we are living. One day, in a moment of clarity, we look around and don't recognize anything about our lives. These things that surround us are not what we want, and worse than that, we don't know what it is that we do want. Once in a Lifetime we all have a choice to make while the days go by. Do we react to the alien life that we discover is ours? Will there be time to do this later? After all, time isn't after us. Time isn't holding us. In the present, there is no time. There is only now. So once in a lifetime is now and it is always now. Also, it is so much fun to sing along and have a good spaz out while listening to the song.