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Frank Cooper Craighead Jr. was born, along with his twin brother John, on August 14, 1916, in Washington D.C. to Dr. Frank C. Craighead Senior and Carolyn Johnson Craighead. Along with their parents and younger sister Jean, Frank and John spent their childhood in the D.C. area participating in many outdoor activities, including fishing and natural history. The long association with the natural world was both a hobby and a passion for Frank and John. Their first turn towards professional was in 1934 when they took a trip out west to Wyoming with friends to pursue their long-time hobby of falconry. The photos and observations of this trip led to their first article "Adventures with Birds of Prey," published in National Geographic in 1937. They published their first book together, Hawks in the Hand, in 1939. Both brothers attended Pennsylvania State University for undergraduate degrees in science and received MS Degrees in Ecology and Wildlife Management from University of Michigan. Both completed their PhDs at the University of Michigan in 1949.

Throughout these years, they continued their own personal work with birds, and their published articles caught the attention of K.S. "Bapa" Dharmakumarsinjhi, an Indian prince who reached out and visited the brothers in the U.S., then invited them to visit his own falconry operation. That year long visit, paid for by the National Geographic Society, created a film about the experience Life with an Indian Prince. Later in life, they also published a book on the visit. They had both started working on their doctorates in 1941, but the outbreak of World War II shifted their plans of study. Although both had intended to enlist in the U.S. Army, the US Navy recruited them to set up a survival training program for pilots and sailors during the conflict. As USNR Lieutenants, they worked in Pensacola, Florida, and also trained with other Navy instructors in the Marshall Islands and Philippines. As part of their work with the Navy, the manual How to Survive on Land and Sea was published. They continued conducting survival training with the Strategic Air Command during the Korean War.

Frank's career first took place outside of formal academia. He worked with the government on classified defense research from 1953 to 1955, then managed the Desert Game Range in Nevada from 1955-1957. In the late 1950s he also worked for the US Forest Service in DC, and from 1967 to 1977, he worked for the State University of New York at Albany. In 1959, the brothers reunited professionally to begin their study of the grizzly bears of Yellowstone National Park. The study, which lasted until 1971, involved the trapping of over six hundred grizzlies. The bears had never been studied to this extent to learn about their habits (food, denning, for example), and it was hoped that this research would help to learn how to manage the bear population as it interacted with humans. John Craighead was first approached about the project, and then he drew Frank into it. Their greatest contribution was the development of wildlife radio telemetry, to create radio collars to be placed on the bears, and then use radio signals and antenna to track their movements to figure out where the bears where going and what effect that had on the bears, people and the park itself. As part of this process, they had to develop techniques to tranquilize the bears in order to put the collars on them without putting the workers in danger from the bear, and vice versa. Because the data showed the bears ranged beyond the park, Frank and John expanded the definition of "Yellowstone" the borders of the 3,500 square mile park to the Greater Yellowstone Ecosystem (GYE) to allow for this movement. This definition means that a 18,750–34,375 square mile area spanning MT, ID and WY, including Grand Teton National Park. This expanded the research focus of their work, and all of the flora and fauna within it. The Craigheads are also well-known for their contributions to the Wild and Scenic Rivers Act of 1968.

Starting in the 1950s the Craigheads went on rafting trips as part of their survival trainings. This led them both to appreciate the beauty and importance of the rivers, and the need to protect them. They wrote an article for Naturalists in 1957 proposing a river classification system to help people better understand this, as well determine where human intervention would help or harm. In 1958, Frank was asked to prepare a paper on this topic to help with the Outdoor Recreation Resources Review Commission, which was set up to study the country's recreation needs and determine how to classify rivers of great scientific and recreational value, among other classifications. He did this via his Outdoor Recreation Institution, collecting a list of 650 rivers to be considered for designation as National Rivers. This was part of the overreaching push for the Wild and Scenic Rivers Act of 1968 to designate and protect rivers. In addition to their work on the grizzlies, they also conducted studies on elk, geese and birds of prey, and published research on these various animals. They became well-known to the world through not only their research, but also the films and photographs they produced featuring their work. Frank also published two books: Track of the Grizzly and For Everything There is a Season.

In 1964, Frank founded the Environmental Research Institute in Moose, Wyoming. The organization grew out of Frank's project, the Outdoor Recreation Institution, which was formed as part of his research into wild rivers. The name of the organization changed to the Craighead Environmental Research Institute, then changed a final time to the Craighead institute. Since its founding, it has designed and managed research projects focused on Greater Yellowstone Ecosystem and the Northern Rockies, and also global projects. Its goal is to research and maintain healthy ecosystems for the people, animals and plants living in them.

Frank married Esther Stevens, with whom he had three children: Lance, Charlie and Jana. In the late 1960s Frank and Esther permanently moved to Moose, Wyoming after years of commuting/traveling to their cabin, and would live there the rest of their lives. Esther passed away in 1980, and in 1987 Frank married his second wife Shirley. Frank passed away in 2001 at age 85 from complications of Parkinson's Disease.