Official tournaments use a set rotation system. This means that only the newest sets are legal for tournament play. Since Pokémon offers tournaments on a very casual level, this is definitely a point to consider.
What sets are currently legal changes once a year, usually around September. Any new set that is released automatically becomes legal (for higher level tournaments such as National Chamionships, there is a small delay between the street date and the date when it becomes legal for tournament play).
Most of the time, the number of legal sets after a rotation occured in September is roughly 5-8. Right before the rotation (at the time the World Championships take place), it's usually 9-12.
The time between 2 rotations is called a Season. All achievements, point scores and similar things connected to tournaments and leagues ("Organized Play"), notably the age group players are assigned, are reset at the start of each Season.
Game Mechanics (rules), while slightly changing with each era (see the other answer), usually stay mainly the same.
Strategic Mechanics, however, generally change a lot between eras. Sometimes, Basic Pokémon play the most important role, sometimes Evolved Pokémon do (right now, as of X&Y, Evolved Pokémon are back on the rise). Searching Pokémon out of the deck is sometimes based mainly on other Pokémon's abilities, other times on Supporters or Items. Some eras have very strong Energy manipulation, others are very disruptive, still others rely on damage manipulation a lot.
Some eras even use completely new mechanics which are not present in older (or newer) sets. An example for this is the Heartgold & Soulsilver era, which introduced the Lost Zone, an area nowhere on the field where cards could never return from (within one game), as well as several cards referring to this area and using it (for example, Lost World allowed a player to declare himself the winner if at least 6 of the opponent's Pokémon were in the Lost Zone, while Mew was able to use any attacks of Pokémon in the Lost Zone). This concept was never used again after Call of Legends.