Performance-enhancing drugs, or PEDs, include all pharmaceutical products considered to give an inappropriate boost to athletic performance, such as steroids, amphetamines or human growth hormone. Their use has been banned by Major League Baseball for a number of years for health reasons, although this ban only became truly effective with the introduction of testing in the Collective Bargaining Agreement in the wake of the 2000s steroid scandal and the BALCO affair. PEDs are not to be confused with drugs of abuse, such as cocaine or marijuana, which are also banned, but whose effect on performance is usually detrimental. Many of the banned PEDs are also scheduled drugs whose possession or distribution without a prescription is a federal offense.
Internationally, PEDs are banned by the International Olympic Committee, which includes testing undertaken by the World Anti-Doping Agency (WADA) as part of competitions it organizes, such as the baseball tournaments at the Olympic Games. The International Baseball Federation has its own testing regime for competitions such as the Baseball World Cup.
A number of prominent players have been suspended for infringing Major League Baseball's policy on PEDs, most notably Rafael Palmeiro in 2005 and Manny Ramirez in 2009. Ramirez was detected through Major League Baseball's systematic testing program which performs approximately 3,600 tests per year, failing a test in 2009 that led to his suspension, and a second one in 2011 that prompted his retirement.
While PEDs were largely accepted by players as a fact of the game in the 2000s, with only a few lone voices speaking out against them, things changed the following decade, as many prominent players began to ask the Players Union to demand more stringent controls and penalties, in order to rid baseball of the taint caused by the benign neglect of its drug problem over the previous two decades. As Ryan Zimmerman put it in 2013: "If you want hardship penalties, I'm all for that. Nobody wants to watch cheaters. Those guys make those of us who don't cheat, don't use, look worse." This coincided with the rise of Michael Weiner, who had long been an advocate for a drug-free sport, as the union's chief.
During spring training in 2013, the major league's next significant PED scandal emerged, when an investigation into a Miami, FL clinic, Biogenesis Laboratories, revealed that it including a number of major league players among its list of clients. The clinic was suspected by Federal authorities of supplying PEDs to its clients. An in-depth investigation of the allegations was immediately launched, and the first suspension was handed out on July 22nd, when Ryan Braun recognized that he had violated MLB's drug program and chose not to contest a suspension for the remainder of the year.
The infamous "steroids" era of baseball was chronicled in a feature documentary film by Billy Corben entitled Screwball, which received its premiere at a film festival in November 2018.
- Christine Brennan: " Crackdown shows tide has turned on MLB dopers", USA Today, July 31, 2013 
- Howard Bryant: Juicing the Game: Drugs, Power and the Fight for the Soul of Major League Baseball, Viking Press, New York, NY, 2005.
- Jose Canseco: Juiced: Wild Times, Rampant 'Roids, Smash Hits and How Baseball Got Big, William Morrow, Harper Collins Publishers, New York, NY, 2005.
- Will Carroll: The Juice: The Real Story of Baseball's Drug Problem, Ivan R, Dee, Publisher, Chicago, IL, 2005.
- Mark Fainaru-Wada and Lance Williams;: Game of Shadows: Barry Bonds, BALCO, and the Steroid Scandal that Rocked Professional Sports, Gotham Books, New York, NY, 2006.
- David J. Gordon: "Did Performance-Enhancing Drugs Prolong Careers?", Baseball Research Journal, SABR, Volume 50, Number 2 (Fall 2021), pp. 140-147.
- Bob Nightengale: "Dirty players, sloppy chemists, or both? Another twist in MLB's PED problem", USA Today Sports, April 26, 2016. 
- Josh Peter: "BALCO figures offer how to rid sports of doping 15 years after scandal", USA Today, September 3, 2018. 
- Kirk Radomski and David Fisher: Bases Loaded: The Inside Story of the Steroid Era in Baseball by the Central Figure in the Mitchell Report, Hudson Street Press, New York, NY, 2009. ISBN 1594630569