The moment when you realize that, while you have friends - and some wonderful friends - you don't have a "buddy". Someone who calls randomly, someone to take off on a road trip with or just go out to dinner with.
It's not necessarily a bad thing - just a kind of sad moment - when you realize it. In my past it's primarily been a spouse or partner but that's no longer the case. Some things are better done with another person. To share the experience and have a commonality of interests. Oh well - doing things periodically alone isn't the worst thing that can happen and it serves to make the shared activities more significant.