Kleiser has directed several feature films, including Grease (1978), The Blue Lagoon (1980) with Brooke Shields, Summer Lovers (1982) with Daryl Hannah, Grandview, U.S.A. (1984) with Jamie Lee Curtis, Flight of the Navigator (1986), featuring the first use of digital morphing in a film, Big Top Pee-wee (1988), White Fang (1991) and Honey, I Blew Up the Kid (1992).
He has taught a graduate workshop at USC and Masters Directing Classes for European students at film festivals in Deuville and Sarlat, and Malaga. He serves as a judge on the Student Awards for the Academy of Motion Picture Arts and Sciences; and, as chairman of the Academic Subcommittee for the Directors Guild of America, he inaugurated a videoconferencing program to connect film classes with working directors. Working with the Graphics Lab at USC's Institute for Creative Technologies, he has co-invented a digital Cinerama-like process called Vistarama HD.