Part narrative, part documentary, and part animation, What the #$*! Do We Know?! was filmed with the intent of expressing the neurological processes and so called "quantum uncertainty" of life. With the help of a directorial triumvirate consisting of Betsy Chasse, William Arntz, and Mark Vicente,
Marlee Matlin stars as Amanda, whose uninspired daily routine is abruptly altered into a chaotic, Alice in Wonderland-style reality, complete with quirky characters and wildly different perspectives on life. As Amanda falls deeper into the experience, she's forced to drastically reconsider her perceptions of interpersonal relationships, men, and the fundamental principles of life. What the #$*! Do We Know?! is supplemented by a host of mystics and scientists, who are interviewed intermittently throughout the film for their wisdom and knowledge concerning religion, science, the thin line between them, and the consequences of blurring that line. ~ Tracie Cooper, All Movie Guide