Gamblers had their name changed to Gamers in this game, as Nintendo didn't seem to want a gambling reference. Yet surprisingly, the Celadon City Game Corner - where you can go in and play slot machines - was left completely intact.
If playing a pirated copy, there is an NPC who will say "If you like this game, buy it or die!"
In the Pewter City Museum, the caption Space Shuttle Columbia was changed to just Space Shuttle because of the crash of the Columbia in 2003, though this remains unchanged in the Japanese version.
In the original Red, Blue and Yellow, the cave leading to Mewtwo would unlock after you beat the elite 4, but in the remake, you have to do that, get the national Pokedex and get the Ruby and Sapphire link from the Sevi Islands before you can enter the cave.
This video game takes place in the Normal Timeline of the Pokémon multiverse, together with Pokémon Versione Verde Foglia (2004), Pokémon Versione Smeraldo (2004), Pokémon versione Platino (2008), Pokémon Oro HeartGold (2009), Pokémon Argento SoulSilver (2009), Pokémon Versione Nera (2010), Pokémon Versione Bianca (2010), Pokémon Versione Nera 2 (2012) and Pokémon Versione Bianca 2 (2012).