Armed with the first overall pick, new team president Bill Polian had two quarterbacks to choose from: Peyton Manning – the son of a former NFL player who starred at the University of Tennessee – or Ryan Leaf, the big man with a strong arm who had decided to leave Washington State a year early to enter the league.
History, of course, tells us the Colts made the correct call.
Manning spent 14 seasons in Indianapolis, his hugely successful spell with the team including leading them to glory in Super Bowl XLI. His jersey number (18) was retired by the franchise, while there is a statue of him at the team's Lucas Oil Stadium.
The San Diego Chargers, meanwhile, claimed Leaf at two. Their marriage did not run so smoothly – or last too long (three seasons, to be precise). He played just 25 games in a career that also included a stop in Dallas, throwing 14 touchdowns and 36 interceptions, and is regarded as one of – if not the – biggest draft busts.
But what if Leaf had gone first instead? Let's start at the beginning…
THE COLTS
Having the first pick was the ideal building block for Polian, who was always going to hand new head coach Jim Mora a rookie QB to work with.
Manning started from the outset with the Colts. There were early teething problems and he finished his debut season with a 3-13 record, throwing more interceptions (28) than touchdowns (26).
However, the chance to learn on the job aided his development. The Colts went on to make the playoffs in the next two seasons and while 2001 was not so successful, a 6-10 campaign led to the arrival of Tony Dungy as head coach and, well, the rest is history.
Whether Leaf would have developed in the same circumstances has to be considered doubtful with how his career panned out, but Indianapolis would have at least afforded him time in which to prove himself.
They also had two rather useful pieces to help, as a running back by the name of Marshall Faulk and a wide receiver called Marvin Harrison were already on the roster.
Had Leaf still flamed out in a similar timeframe with the Colts – it should be pointed out he missed his second season in San Diego through injury - they may well have used the 2001 draft to find a replacement. The Chargers did exactly that, using the 32nd pick on Drew Brees.
THE CHARGERS
Here is where an alternative NFL timeline gets seriously interesting.
Manning as a Charger may not have blossomed in time to keep head coach Kevin Gilbride in a job – he was fired midway through the 1998 season, his second at the helm – but he may well have been the key to keeping the team in San Diego.
Owner Dean Spanos moved the Chargers to Los Angeles after an unsuccessful attempt to get a new stadium built. A failure to secure tax-payer funding led to relocation in 2017.
Surely, though, the presence of Manning could have made a difference. On-field success - perhaps even a Super Bowl triumph like the one the Colts enjoyed - could have led to them getting the backing required to stay put.
Instead, L.A. is now home, though they have so far struggled in competition with the Rams to attract fans. There have even been rumours that the Chargers could move again soon, this time overseas to become the NFL's permanent residents in London.
And what of Brees? Manning's presence would have made picking another QB a waste of draft resources. In 2001, the team to next take a player at the position after the Chargers were the Cowboys, meaning Drew could well have gone on to become a star in Dallas instead.
THE 2004 DRAFT
Of course, there is another Manning whose career would have changed if you take a sliding doors approach to the '98 draft.
After life with Leaf failed to pan out, the Chargers had better luck with Brees before then moving on to Philip Rivers.
However, they selected Peyton's younger brother Eli with the first pick in 2004, rather than Rivers, even though the former Ole Miss quarterback never had any intention of playing for them.
Eli ended up in New York with the Giants in a trade that saw Rivers, who was drafted at four, head in the opposite direction. The next QB taken that year? Ben Roethlisberger, who went to the Pittsburgh Steelers at 11. The Buffalo Bills also used their first-round pick on the position, opting for J.P. Losman after moving up to 22.
Yet had Peyton's place been in San Diego, several notable signal callers selected early in 2004 could have ended up in different locations to begin their pro careers.