Typically, you "draft" a bunch of players, either live (meaning you handpick one player each round) or automated (in which you organize players in a list, and each round the computer picks the highest-ranked player left on your list while making sure your needs are filled so you don't end up with, like, half your team as quarterbacks

); with automated, there's usually a pre-made list that you can customize and slide players up and down rather than having to build the whole list from scratch.

Then you plug in who you think are the best players on your team each week and try to get the most points, with those points coming from things like touchdowns, yardage, number of catches, etc.
You can change your team throughout the year by picking up players no one else has on their team, or by trading (if people are nice enough to accomodate). With football, unlike other sports, there is only one game for each NFL team any given week, so you have several days in between to plan, make changes, and get your team locked in before the next set of games.
Each week, you would go head to head with one of your fellow TLHH member's teams, and whoever gets the most points that week wins.
It's a little complicated, but LOTS of fun and easy to pick up quickly. You don't even have to know much about the sport, since most good systems will make recommendations on who to play each week and tell you about all their stats to date and such.
Hope that helps.