One of 30 named islands in the Shumagin Group, Simeonof Island was established as a refuge for sea otters in 1958. It became a Wilderness in 1976 and a subunit of the Alaska Peninsula Unit of the Alaska Maritime National Wildlife Refuge in 1980. Refuge "lands" include the water, shoals, and kelp beds within a mile of the island where at least 17 species of whales have been identified (minke whales are the most common), but where surprisingly few sea otters still live. With shores that slope easily to the sea and wide beaches, Simeonof attracts relatively few seabirds. Three streams support salmon.

Cattle and fox ranchers used the island between 1890 and 1930, but they eventually abandoned their ranches. Cattle were returned to the island in 1960, and a herd that was often too large for the island to support scared off the few terns and other birds that nested here. In 1985 the last cow was removed, and a resurgence of bird life is expected.

With a well-protected harbor offering safe anchorage, Simeonof Island lies 58 miles from the mainland and is difficult to reach. Rain, fog, strong winds, and cool temperatures descend on the island, which receives few human visitors. Those who do visit come primarily to see a truly wild piece of earth, and perhaps a few whales. All are asked to leave the wildlife strictly untouched.