Fatigue is a common issue that happens to players in this game just like the real world. They need to be rested from time to time. The biggest complaints takes place in the minors with pitchers. The objective is to have them play at 100%. Minor rosters have 25 active players just like the majors but can have 10 or more on the inactive roster. Two or three extra pitchers is always helpful regardless of how ugly they are. This allows you to swap players out if needed for a rest. Position players also get tired so it isn't just the pitchers. Fatigue on players run a higher risk of injury and his playing abilities diminishes.
For a pitcher, Stamina is the driving factor as to how many pitches can be thrown in an outing but differs between the different types of pitchers. Durability is used as the rate of recovery. The lower the Durability the slower the recovery. Most of your time will entail going through each pitching roster and resting pen pitchers after each game. Tweaking the TPC and MPC usually eliminates the need for extra days for starters. For a newbie it is tough until you get the hang of it. But be warned, if a pitching staff gets to 0%, recovery is very tough.
Fatigue on position players is different. It is based on the number of AB's. The formula: 730 x Durability% gives the number of AB's a player can roughly have in a season without fatigue being an issue. Basically they use a formula that projects a players number of AB's with his batting slot and when the number is exceeded fatigue sets in. Roughly, a player with a 70 durability needs about 15 to 20 games off throughout the season where an 80 durability needs about 12 to 15 games off. Usually you don't have to worry that much about position players with a durability above 85. Also remember that players in the first 4 slots in the batting order will get more AB's in a season.
It was noticed last season in both of my worlds that certain young players at the ML level never fatigued, not sure why.