Originally a humble and content medical doctor with a loving wife and a beloved son, Van Richten's life was changed forever one evening when a band of Vistani burst into his house and demanded he treat one of their members, who was severely injured. In fact, he was too badly injured for Van Richten to save him. As he died, the doctor begged for the Vistani not to hurt him, as he knew and feared their dark magic and vengeful curses, offering to give them whatever they wanted in exchange for mercy.
Unfortunately for him, these Vistani had been hired by a gay vampire, a Baron Metus, to find him a handsome man to turn into his "Companion" (a special kind of vampiric spawn with a telepathic link). They had tried to kidnap a nobleman's son beforehand, which hadn't worked out; that's why the one Vistani was killed. So, they promptly kidnapped Van Richten's son to give him to Metus. Vistani are dicks like that.
Needless to say, daddy Van Richten was pissed when he figured this out, and he chased off after them. Along the way, he crossed into Darkon, where he, by sheer good fortune, ran into its Darklord, the lich-king Azalin Rex. Amused by Van Richten's tale, and not liking the special snowflake gypsies himself, Azalin gave Van Richten an army of zombies for his protection and pointed him on his way. Van Richten soon caught up to the Vistani tribe he was after, surrounding them with his undead minions and demanding they give him back his son. The Vistani's leader, one Madame Radanavich, gloated that they already gave him to Metus. Furious, Van Richten unleashed the zombies on the Vistani, with Radanavich cursing him to have everyone he held dear be killed by monsters before she was torn apart and eaten alive.
Next, Van Richten went after Metus, who rebuffed him when he demanded to see his son. But junior Van Richten crept out of Metus' mansion that night to see his dad - alas, Van Richten was too late; he was already a vampire. The two shared one last night together, and then Van Richten staked his son and burned him in the rising sun. When he finally returned home, he discovered to his horror that Metus had slain his wife in retaliation, using the Mists and his own powers to get ahead of the doctor. Outraged and grieving, Van Richten swore to destroy Metus and all of his kind, and soon made good on his vow by slaying Metus.
Van Richten literally wrote the manual on hunting the vampire, the lich, the ancient dead, the ghost, the werebeast, the fiend and even the Vistani - although, in that one, he actually came around to say that the Vistani really aren't all bad and you should only hunt them down if they deserve it.
In-universe, Van Richten mysteriously disappeared- this is an oblique reference to the Bleak House adventure boxed set, in which he sacrificed himself to defeat the ghost of Madame Radanavich, who sought to imprison the spirits of his former companions with the aid of the resurrected Baron Metus. His legacy was taken up by the daughters of one of his friends, the Weathermay-Foxgrove Twins. This is why Van Richten's Guide to the Witch (and Hags) was only published as part of the third "Van Richten's Monster Hunters Compendium", being based on them putting together all of the notes he had found for it and releasing it. They went on to publish their own guides under Van Richten's name, covering the Walking Dead, the Shadow Fey and The Mists (which was never printed, because the license ran out, but was released online).
5th edition gives him a cameo in Curse of Strahd under the pseudonym of "Rictavio", with several changes to his backstory. Notably, he now is fully aware of his curse and did not entirely wipe out the Vistani clan who kidnapped his son. Indeed, one of them later met with him to admit her own misgivings about the clan's actions and served as his apprentice for a time.