The Peale family is best known as a family of artists; however, family interests and activities were much more wide-ranging. The best known Peale is Charles Willson Peale (1741-1827, APS 1786), who produced more than one thousand paintings, including hundreds of portraits of leading Americans during the colonial and early national periods. Peale was married three times, to Rachel Brewster (1744-1790), Elizabeth de Peyster (1765-1804), and Hannah More (1755-1821). He had eighteen children, eleven of whom reached adulthood. Three of Charles Willson Peale's sons became artists: Raphaelle Peale (1774-1825), Rembrandt Peale (1778-1860), and Rubens Peale (1784-1865). A fourth son, Titian Ramsay Peale (1799-1885, APS 1833), was a naturalist (who made drawings on the exploring expeditions he accompanied) and pioneer in photography, and another son, Benjamin Franklin Peale (1795-1870), became a naturalist and paleontologist. Peale's daughter Sophonisba Angusciola was married to Coleman Sellers (1781-1834), an inventor and manufacturer of machinery, including locomotives. Two of their sons, George Escol Sellers (1808-1899) and Coleman Sellers (1827-1907, APS 1872), were inventors and engineers. The latter served as director of the construction of the hydro-electric power development at Niagara Falls. He was married to Cornelia Wells Sellers (1831-1909). One of their grandsons was Charles Coleman Sellers (1903-1980, APS 1979), a librarian and historian and the author of several studies of the Peale family, including a Charles Willson Peale biography.

Though the Miscellaneous Manuscripts collection is composed of items that do not fall readily into any other existing collection, the two dominant intellectual areas represented in the collection are Early American History and History of Science.