The "Hands of Blue" were a pair of mysterious men, who wore suits and blue gloves. They were contractors to the Union of Allied Planets (believed to be from the Blue Sun Corporation) who monitored the security of former students of the Academy and were in pursuit of River & Simon Tam. Anyone who had any form of contact with River, even Alliance personnel, were killed without mercy with the use of a sonic device that induces massive bleeding from every orifice.
Two female Hands of Blue boarded the Sun Tzu when Silas escaped his confinement there. They captured and interrogated Simon about River's whereabouts and her connection with Silas.
The Hands of Blue always appear in pairs, each of the two organisms possessing a shared consciousness. When Silas kills one of the two female hands of blue, the other loses her ability to fully function, and kills herself and the rest of those aboard the Sun Tzu out of depression.
The pair are never officially named in either Firefly or Serenity. In "The Train Job" DVD commentary, Joss Whedon refers to them as "the men with blue hands" and "the blue-hands men". IMDb's cast listings name each of them as a "Blue Glove", perhaps the most accurate moniker. However, "Hands of Blue" seems to have become a fanon name for the otherwise unnamed pair, from River's "two by two; hands of blue;" litany (possibly in reference to there being four blue-gloved hands between the two men, or to the fact that the men are merely one pair and may be followed by more like them, and the double-meaning for blue, as in, hands of Blue Sun.)
In the Serenity comics, the blue "gloves" are shown to extend to and cover the upper body as well. They were finally killed when Serenity's engine flare incinerated them, and the Alliance passes the assignment to retrieve the Tams to the Operative, explaining why it is he and not they in the movie Serenity who is chasing them.
It is possible that they are cyborgs, as Hands of Blue 1's upper body looks metallic and appears to have screws in it; also, this would explain their immunity to their own device. Blue 1, in the television episodes, has a stiff, mechanical quality to his movements, and his whole face is held rigidly in place most of the time.
The rhyme by River was even referenced in the TV show Castle, in hand actions made by Nathan Fillion's character, the eponymous Richard Castle, at a crime scene when he himself dons blue gloves to avoid contamination.
- Dennis Cockrum and Jeff Ricketts also appeared in the TV series Charmed (which has a similar style to the Joss Whedon series Buffy the Vampire Slayer, in which Jeff Ricketts also appeared), though in different seasons and completely different roles (Jeff Ricketts plays a Horseman of the Apocalypse in Season 2, while Dennis Cockrum plays a used car salesman in Season 8).