The two-time American League Cy Young Award winner and three-time All-Star has emerged as the poster child for the annual event, which will take place Thursday at the Baseball Winter Meetings in Las Vegas.
But if you look at the numbers he posted in 2000, when the Minnesota Twins tucked him into a situational role in their bullpen in order to keep his rights, Santana hardly put up numbers worthy of, say, a Johan Santana.
After he posted a 4.66 ERA at Class A Michigan in 1999, Santana was left unprotected by the Houston Astros and was taken with the second selection in the December draft, landing with Minnesota via a prearranged Rule 5 pick trade.
That summer, the southpaw went 2-3 with a 6.49 ERA in 30 games, including five starts, with the Twins. He allowed 102 hits in over innings, walking 54 while striking out 64 as opponents hit .302 against him. Santana's numbers in the bullpen in 2001 weren't that much better as he posted a 4.74 ERA in 15 appearances.
In fact, it wasn't until 2002, when he spent the first two months of the season perfecting his changeup at Triple-A Edmonton before rejoining Minnesota, that the Venezuelan began to show why he was worth the Twins' patience.
Santana posted a 2.99 ERA in his return to the big leagues that year, and the rest is history.
So it's too early to say that none of the 18 players taken in the Major League phase of the 2007 Rule 5 Draft will ever approach the bar set by Santana. That said, only one of the 18 has spent an uninterrupted full season in the big leagues.
Left-hander Wesley Wright -- the eighth player selected last winter -- made 71 relief appearances for the Astros, posting a 5.01 ERA and limiting big league hitters to a .214 average. He averaged 9.22 strikeouts per nine innings and is the lone member of his Rule 5 class to be close to a lock for a 2009 job.
Three other players -- St. Louis Cardinals outfielder Brian Barton, Baltimore Orioles reliever Randor Bierd and Seattle Mariners right-hander R.A. Dickey -- spent most of last season in the Majors with their new organizations, but with caveats.
Of that trio, only Barton remains on a 40-man roster. The versatile outfielder, originally signed by Cleveland as a non-drafted free agent out of the University of Miami, spent several weeks on the disabled in '08. When healthy, he hit .268 with two homers and 13 RBIs in 82 games for the Cardinals.
Taken with the 10th pick in the Rule 5 Draft, it is widely assumed that had Barton remained in good health, he either would have gone much higher or would have been protected by the Indians.
Bierd, selected by the Orioles out of the Tigers system with the third pick in the draft, also had a two-month stint on the disabled list with shoulder trouble. He posted a 4.91 ERA in 29 games but was outrighted off Baltimore's 40-man roster in mid-October and is eligible again for the Rule 5 Draft.
Seattle completed a preseason trade with the Twins to retain Dickey's rights and sent him to the Minors to open 2008. But they brought back the former first-rounder, who has added a knuckleball to his repertoire, in late May and he posted a 5.21 ERA in 112 1/3 innings with the Mariners.
Dickey was 33 years old when he was taken in the Rule 5, proof the process is not just about finding overlooked "kids." Taken with the 12th pick, he also looked like he'd be one of only six 2007 Rule 5ers (along with Wright and Barton) to head into this year's draft protected on a big league roster. However, the Mariners outrighted Dickey (along with 2006 Rule 5 pick Sean White) to the Minors just days before the Winter Meetings began, clearing room on their 40-man roster.
Of those half-dozen players, the other three who will be exempt from this year's draft are right-handers Evan Meek, Randy Wells and Steven Register.
Meek, taken with the second overall pick by Pittsburgh from Tampa Bay, posted a 6.92 ERA over 13 innings with the Pirates but cleared waivers before combining for a 2.51 ERA between Double-A Altoona and Triple-A Indianapolis. Knowing firsthand that a youngster with that kind of stuff will attract interest in the Rule 5, the Pirates decided to add him to the 40-man roster this fall.
Wells and Register, however, head into the 2008 draft on the 40-man rosters of the clubs that lost them in last year's Rule 5, proving the "fool me once, shame on you" aspect of this event. Both finished the 2008 season in the big leagues with their respective clubs.
Wells, taken 11th by Toronto from the Cubs, appeared in one game with the Blue Jays before being returned to Chicago's system. He went 10-4 with a 4.02 ERA at Triple-A Iowa and was promoted to the Majors in September, tossing 5 1/3 hitless innings over three outings.
Register, selected by the Mets with the 13th pick from Colorado, was returned to the Rockies organization, where he posted a 3.36 ERA and 16 saves for Triple-A Colorado Springs. Called up for the last month of the season, he remains on the Rockies' 40-man roster.
Among the other 11 players drafted last year, eight eventually were returned to their original clubs, including 6-foot-6 right-hander Tim Lahey, the first player taken. The Princeton University product, plucked out of the Minnesota system by Tampa Bay and dealt immediately to the Cubs, finished with a 5.18 ERA at Triple-A Rochester, then posted a 3.97 mark for the Arizona Fall League champion Phoenix Desert Dogs.
Also returned from whence they came: No. 4 LHP Jose Capellan (Boston); No. 6 RHP Sergio Valenzuela (Atlanta); No. 7 3B Matt Whitney (Cleveland); No. 9 RHP Fernando Hernandez Jr. (White Sox); No. 14 RHP Michael Gardner (Yankees); No. 17 IF Callix Crabbe (Milwaukee); No. 18 RHP Lincoln Holdzkom (Boston).
Three other Rule 5 picks had their teams either send them down when no one claimed them off waivers or strike deals to retain their rights before sending them down: No. 5 RHP Carlos Guevara (San Diego from Cincinnati); No. 15 LHP Travis Blackley (Philadelphia from San Francisco); No. 16 OF Garrett Guzman (Washington from Minnesota).
Lisa Winston is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.