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Landon was born Eugene Maurice Orowitz on October 31, 1936, in Forest Hills, a neighborhood of Queens, New York. His parents were Peggy (nee O'Neill; a dancer and comedian) and Eli Maurice Orowitz. Eugene was the Orowitz family's second child; their daughter, Evelyn, was born three years earlier. In 1941, when Landon was four years old, he and his family moved to the Philadelphia suburb of Collingswood, New Jersey.

The year after Bonanza was canceled, Landon went on to star as Charles Ingalls in the pilot of what became another very successful television series, Little House on the Prairie, again for NBC. The show was taken from a 1935 book written by Laura Ingalls Wilder, whose character in the show was played by nine-year-old actress Melissa Gilbert. In addition to Gilbert, two other unknown actresses also starred on the show: Melissa Sue Anderson, who appeared as Mary Ingalls, the oldest daughter in the Ingalls family, and Karen Grassle as Charles' wife, Caroline. Landon served as executive producer, writer, and director of Little House. The show, a success in its first season, emphasized family values and relationships. Little House became Landon's second-longest running series.  The show was nominated for several Emmy and Golden Globe awards. After eight seasons, Little House was retooled by NBC in 1982 as Little House: A New Beginning, which focused on the Wilder family and the Walnut Grove community. Though Landon remained the show's executive producer, director and writer, A New Beginning did not feature Charles and Caroline Ingalls. A New Beginning was actually the final chapter of Little House, as the series ended in 1983. The following year, three made-for-television movies aired.  Melissa Gilbert said of her on- and off-screen chemistry with Landon, "He was very much like a 'second father' to me. My own father passed away when I was 11, so, without really officially announcing it, Michael really stepped in." When not working on the Little House set, Gilbert spent most of the weekends visiting Landon's real-life family. She once said, "The house was huge. We ran like banshees through that house, and Mike would hide behind doorways and jump out and scare us." In a 2015 interview, Gilbert said of Landon, "He gave me so much advice...the overall idea that he pounded into me, from a little girl, into my brain was that nothing's more important than 'Home & Family'; no success, no career, no achievements, no accomplishments, nothing's more important than loving the people you love and contributing to a community. Though we were working, really, really hard, we were 'Not Saving The World', one episode of television at a time, we're just entertaining people and there are more important things to do.... and have fun; no matter what."
Michael Landon