It's not to hard to see that Rob Lowe is one of the busiest men in Hollywood ... But at home, his life is a lot more simple, as he's had wife Sheryl Berkoff beside him for almost four decades.

Related: Rob Lowe doesn't get why Nicole Kidman's Babygirl ... by moving his family (also including wife Sheryl Berkoff, whom he married in 1991) outside of Los Angeles years ago.

Rob Lowe couldn't help but agree with the sentiment ... "That's the queen. Go against my wife? Good luck. I don't even need to get involved." Cameron Diaz and Benji Madden were married in 2015.