A notorious undisciplined hitter, Guillén is prone to long slumps, but will usually make up for them with his hot streaks. As a runner, he has decent speed, but is not much of a threat to steal. He is a below-average fielder, but his arm is strong as the best and his range is decent.

In 2004, Guillén hit .294 with 27 home runs and 104 RBI for the Angels, but he was suspended the last two weeks of the regular season and during the postseason for "inappropriate conduct" in publicly expressing his displeasure with Angels manager Mike Scioscia following Scioscia's removal of Guillén in favor a pinch runner during a crucial game against the Athletics.

On November 19, 2004, he was traded to the Washington Nationals for shortstop Maicer Izturis and outfielder Juan Rivera. The move sent Guillén to his sixth team in just five seasons.

In 2005, Guillén began his season strongly. In April, he batted .303 with 6 home runs and 14 RBIs. The Nationals were impressed and on April 29, they exercised his option for 2006. The much traveled Guillén said, "I feel like Washington is my home and hopefully, this is my last stop."

On June 14, 2005, the Nationals began a three-game series against the Angels, still helmed by Mike Scioscia. This marked Guillén's first return to Anaheim since being traded. Going into the series, both Guillén and Scioscia kept a civil tone publicly, each indicating that the past was behind them and claiming that they held no hard feelings toward one another. However, the tensions below the surface were exposed when, during the second game of the series, Angels pitcher Brendan Donnelly was found with illegal substances on his glove.

Donnelly was ejected from the game, and Scioscia then came out of the dugout and exchanged hostile words with Nationals manager Frank Robinson, who had instigated the search of Donnelly's glove. The confrontation led to both teams' benches being cleared as all of the players streamed out on to the field. As he was being restrained by fellow Nationals players, Guillén shouted angry words at the Angels, a number of whom made it clear that they felt their former teammate had been the one who told Robinson to have Donnelly's glove examined. (Several weeks later, Guillén would acknowledge that he had indeed done so.)

In the eighth inning of the same game, Guillén hit a two-run home run to tie the game, and the Nationals went on to win. After the series' final game, Guillén blasted Scioscia and acknowledged that despite his earlier statements to the contrary, he was in fact still hurt over what had happened at the end of the 2004 season.

I don't got truly no respect for anymore because I'm still hurt from what happened last year . . . Mike Scioscia, to me, is like a piece of garbage . . . He can go to hell . . . I can never get over about what happened last year. It's something I'm never going to forget. Any time I play that team, Mike Scioscia's managing, it's always going to be personal to me.

- José Guillén as quoted by Barry Svrluga of the Washington Post on June 16, 2005 Nevertheless, Guillén remains as a crucial ball player for the Washington Nationals. In 2005, he hit .283 with 24 home runs and 76 RBI for Washington. In 2006, he was involved in an incident with Pedro Martinez. Martinez hit him with a pitch twice, and after the second time Guillen charged the mound, only to be held back by Paul Lo Duca and umpire Ted Barrett.