Injuries
Injuries are a part of football (unless you specifically disable them in your league settings), and some injuries are worse than others. On default settings (with the Injuries slider set to 40), you'll have an injury or two per game, and about six to eight per year that will last longer than a couple games. You can view all current injuries for your team with in Injury Report option in the My Team tile.
If a player is injured at all, he can be placed on the Injured Reserve list, usually shorted to the IR. Players on the IR are generally restricted from returning to play for the rest of the season, but their salary is free from the cap without penalty, allowing you to sign a free agent to take his place. You can place an injured player on the IR from his player card regardless of how much time is left on said injury.
During gameplay, a pop-up will tell you how severe a potential injury is and, if the player can return to the game, will ask whether you want him to do so. Doing so usually means you'll field a stronger player, but it brings a chance of re-injury, and that's usually a much worse injury than what you would have had if you just benched him. It's usually best to let the substitute stay in the game; the injured player may come back after some time resting on the sidelines anyway. In the playoffs though, especially if the injury is to a superstar, it may be worth the risk to have him play anyway.
When a player's injury runs its course, there is a chance the doctors will clear him to play, or the doctors may clear him to play early. In the latter case, you'll be prompted on the main menu with a "Big Decision" tile, which has you choose whether you want to have him play through it. This also brings a very high risk of re-injury and is not advised unless it's a superstar you need in the playoffs. Starting the bench player results in more XP too, so it's usually in your best interest to rest the injured player until he's fully cleared, especially since he'll be operating with less than optimal attributes.
As unethical as it is to say, you can exploit the injury system if you have a highly paid player who isn't pulling his weight but is locked into an expensive contract. If he's injured, even if it's just for a week or two, you can place him on the IR and get his money back. It can help you short-term, especially if he's in the last year of his contract, but be careful you don't sign too many expensive players with the new funds since it will come back to bite you in the off-season.
Players placed on the IR early in the season may be eligible to come back if certain conditions are met. If they qualify to be returned later, the "Return" column on the injury report will be marked with "Yes" for them. If you return them to the active roster, their salary will be reinstated, so you may need to make some cuts if you signed expensive players in the interim.