There are currently two popular defensives in the NFL, confusingly called the 4-3 and the 3-4. These defenses are quite different, with different strengths and weaknesses. The numbers refer to the number of down linemen and linebackers. A down lineman is a guy who has a hand on the ground just before the ball snaps. Having a hand on the ground lets him drop his hips lower and get a better drive against an offensive lineman, however it also limits his view of the play and his ability to react to the sides.
Normally, a defense has several down linemen on the field to compete directly with the offensive linemen, and several linebackers on the field, to compete with the tight end, fullback, and running back. The defensive linemen will have a hand on the ground, preparing to do battle with a 310 pound offensive lineman. The linebackers will be standing up, preparing to read the play and react to the actions of the tight end, fullback, running back, and quarterback. In the 4-3 defense, you use four defensive linemen and three linebackers. In the 3-4 defense, it's three defensive linemen and four linebackers.
In the basic 4-3 defense shown above, we have four down linemen: two Defensive Tackles (DT) and two Defensive Ends (DE). Behind these guys we have three linebackers, the Strong Side or Sam Linebacker (SL), the Middle or Mike Linebacker (ML), and the Weak Side or Will Linebacker (WL). Strong Side means the side of the offense that has the tight end, normally on the Defense's left.
These guys each have a job to do, and the job depends on how they read the play. Frequently in a 4-3 defense, the DTs will have one gap responsibility. That means the DTs line up on the shoulder of their man, not head to head, and attempt to get by him and into the backfield. They are responsible that no running back comes through their gap. In the picture above, the gaps are lettered "A," "B," and "C." The positions where the DTs can line up are numbered 1 through 6. Normally in a 4-3 you will have on very large DT who weighs about 330 to 360 pounds. He will line up on the Center's shoulder and handle an A gap. This large guy is called a Nose Tackle (NT). You will often have a second DT who is just a little smaller and faster, perhaps 305-320 pounds, who will line up on the outside shoulder of the right guard in the 3 position. This DT is sometimes called a "3-technique" because of where he lines up. He will have responsibility for a B gap.
There are two more down linemen on the outside of the defensive line. These are the Defensive Ends, or DEs. Their job is to get into the backfield and make life miserable for running backs and quarterbacks. These guys are normally a bit lighter than the DTs, perhaps 285 to 300 pounds. The DEs are supposed to be much faster than the DTs and better at slipping past 320 pound offensive tackles whose only purpose in life is to stop them. The two defensive ends will line up a bit wide. They want to avoid all blocks and get into the offensive backfield as quickly as possible.
If the play is a passing play, these four guys are supposed to disrupt the quarterback, and if possible tackle (sack) him. The offensive tackles will quickly step backwards when the ball is snapped and try to stay between the DEs and their quarterback. The quarterback will normally step backwards too, making a very appetizing looking target. If one of the DEs is quick enough to get past his offensive tackle, the quarterback will normally see this and try to step forward towards his center and two guards, thereby getting out of the way of this very large and unfriendly person. This is where the nose tackle and 3-technique come in. If they are doing their jobs, the nose tackle has pushed the center backwards almost to the quarterback and the 3-technique has almost gotten past his guard to get to the quarterback. If this has happened, the quarterback has no where to go, so something very bad is about to happen to him. If your four down linemen can consistently rush and disrupt the quarterback without any help from the rest of your defense, the offensive team is in real trouble.
If the play is a passing play and the four down linemen are good at their jobs, then the three linebackers will step backwards and protect the middle of the field from short passes. The strong side linebacker will try to block the tight end so that he cannot run across the field and be a useful receiver. If he fails to block him, then he will run alongside him to try to knock any passes down or tackle the tight end immediately if he should catch a ball. The weak side linebacker will often have to follow the fullback or running back, who will most likely be running out of the backfield to be available to catch a pass. It's the weakside linebacker's job to make sure this doesn't happen. The middle linebacker will watch the play develop and get himself into the most disruptive position he can find, covering and threatening any receivers who dare to step into his domain. Middle linebackers make poor neighbors, as they are known to enjoy torturing small animals like your pets.