In 1993, he founded the search engine Infoseek, which in 1999 was sold to the Walt Disney Co.[3][4] He co-founded Frame Technology Corp., bought by Adobe in 1995.

[10] Sometime before March 2021, Kirsch started M10, which markets blockchains for banks, but the board asked him to step down in the summer of 2021 amid controversy generated by his statements on COVID treatments and vaccines.

[11][12] Kirsch, frustrated that CETF's scientific advisory board was not willing to promote use of the drug based on results of a small preliminary study, wrote a post on Medium titled The Fast, Easy, Safe, Simple, Low-Cost Solution to COVID That Works 100% of the Time That Nobody Wants to Talk About.

[11] Kirsch also refused to accept the outcome of a CETF-funded study on hydroxychloroquine, which had found the drug ineffective; he eventually warred with CETF's scientific advisory board over CETF's treatment of both drugs to the extent that in May 2021 all 12 members resigned.

[19][20] Foundation advisors include Robert Malone, Peter McCullough, and Stephanie Seneff.

Before this, in June 2021, Kirsch had appeared with Malone on the Bret Weinstein and Heather Heying podcast, which according to MIT Technical Review "introduced Kirsch to followers of the 'intellectual dark web'" and allowed him to access a "large and receptive audience to his claims about a fluvoxamine conspiracy".