When Vash's bus runs across Wolfwood's motorcycle in the middle of the desert. He proves to be a valuable ally although his and Vash's philosophies often conflict, Wolfwood being a firm believer in martialism while Vash is a pacifist. By the end of the series, he agrees with Vash's way of thinking even though it costs him dearly. Wolfwood's purpose is to raise money for the children in the orphanage he runs.

The giant cross that he carries comes in two versions. Version 1 holds 12 pistols (across arms of the cross). Version 2 houses a giant machine gun (long part of the cross) and finally, a rocket launcher in the top, while the ammunition is stored in the arms of the cross(an alternate opinion is simply that one of the horizontal arms holds ammo for the machine gun and rocket launcher while the other holds six pistols). The trigger for the Version 2 is a skull shaped symbol in the centre of the cross. As can be expected, the weapon/case is very heavy, and only Wolfwood, Milly, and Vash seem to have no trouble holding it (though Vash once comments on its weight). The weapon is not actually named in the anime, but it is commonly referred to as Punisher, which comes from the manga. Wolfwood states that it's heavy "with God's mercy," a fitting statement from the cynical Wolfwood.

He is modeled on Tortoise Matsumoto, the lead singer of the Japanese rock band Ulfuls. The name Wolfwood (ウルフウッド urufuddo) is a corruption of Ulfuls (ウルフルズ urufuruzu), which is in turn a corruption of the English word soulful (ソウルフル sōrufuru).

Nightow is frequently asked in interviews and at convention panels what the "D." in Wolfwood's name stands for. His responses have varied each time, ranging from "Dangerous" to "Dokonokuminomonjawaresumakinishiteshizumetarokakora." The latter is actually stereotypical yakuza slang, and would be written out as "どこの組の者じゃ、われ！？　簀巻きにして沈めたろか、こら！", which roughly means "What the hell family do you think you're from!? I'm gonna tie you up in a reed mat and dunk ya!". The common theme in these various expansions of the single letter "D" is one of destructive force, anger, or violence, which are traits Nightow has modeled the character after.

In the original Japanese version, Wolfwood speaks in a Kansai Dialect. Nightow has said of this: "It's an English-speaking world, so he's not actually speaking Kansai dialect. Think of it as indicating some accent."

(Source: Answers.com, Wikipedia, Nicholas D. Wolfwood)