Selig asked MLB executive vice president of labor relations Rob Manfred to enter talks with Michael Weiner, MLB Players Association executive director, about introducing a tougher anti-doping regime.
"If people want to continue to do what they shouldn't do, then the one thing that you have to do is you have to have stricter penalties. It's as simple as that," Selig told reporters.
"I've always wanted (fans) to understand that I'll always regard cleaning up this situation as something I'm very proud of.
"But you've got to work at it, you've got to work at it every day. You can never rest, because certainly the chemists aren't resting."
The MLB drugs testing program is the strictest of major sports in the United States and recently added blood tests and baseline testosterone readings.
Currently players who test positive for a banned substance receive a 50-game suspension. A second positive test results in a 100-game suspension, and players caught a third time receive a lifetime ban.
The World Anti-doping Agency, by comparison, recommends two-year bans for first offences, with subsequent offences incurring four-year or life bans, though punishments can be lessened subject to conditions.
Seven Major League players were suspended for testing positive to performance-enhancing drugs in 2012, including All-stars Marlon Byrd, Melky Cabrera, Bartolo Colon and Carlos Ruiz.
Former Boston, Los Angeles and Tampa Bay hitter Manny Ramirez and former Mets and Giants pitcher Guillermo Mota remain the two players caught twice and given 100-game bans.
The current MLB regime runs through 2016 but Selig suggested change would be coming.
"I promised myself that I wouldn't get in the way of what Rob and Michael do, but I would change everything," Selig said.
"Change is always inevitable. You see how a program works. The program is working fine, but I've come to the conclusion, the more I've thought about this, that obviously there's some people, a small minority, who need to be given a tougher lesson."
- Sports & Recreation