From her earliest aerial photographs to her images of museum displays, anatomical models, and fashion shows, much of Leonard's work reflects on the framing, classifying, and ordering of vision. She explained in a recent[when?] interview: "Rather than any one subject or genre (landscape, portrait, still life, etc), I was, and remain, interested in engaging a simultaneous questioning of both subject and vantage point, the relation between viewer and world — in short, subjectivity and how it informs our experience of the world." Leonard was active in AIDS advocacy and queer politics in New York in the 1980s and 1990s. In 1992 she wrote "I want a president", a poem inspired by Eileen Myles's run for president. In 1995 she staged an exhibition at her studio on the Lower East Side of Manhattan which featured the work Strange Fruit, an installation of various fruit skins (oranges, bananas, grapefruits, lemons) that Leonard saved and then sewed together by hand with wire and thread. Strange Fruit grew out of a deeply personal response to the losses of the AIDS epidemic and as a meditation on mourning, it became a seminal work of the 1990s. Strange Fruit was exhibited in 1998 at the Philadelphia Museum of Art, where it currently resides. During the mid-1990s Leonard spent two years living in a remote part of Alaska, an experience that influenced much of her later artwork, which often foregrounds relationships between humans and the natural world. Trees are a motif in Leonard's work: examples include a "reconstructed" tree that she installed in Vienna's Secession in 1997 as well as numerous photographs of urban trees mangled in chain-link and razor wire fences. Between 1998 and 2009, Leonard worked on Analogue, a monumental project consisting of an installation of 412 C-prints and gelatin silver prints (in the collection of The Museum of Modern Art, New York, and the Reina Sofia, Madrid), and a portfolio of 40 dye-transfer prints. Influenced by Eugène Atget and Walker Evans but born out of a 21st-century reconsideration of the role of photography, Analogue explores transformations in global labor, trade, and social relationships in parallel with the shift from analog to digital image-making. Holland Cotter described an experience of the work in The New York Times in 2009: "In her straight-ahead photographs of storefronts, an arrangement of shoes or shrink-wrapped furniture becomes a vanitas still life. A hand-painted shop sign becomes a relic. Over several photographs, we sense that an unnamed neighborhood — Ms. Leonard expanded her field work to include East Harlem, Bedford-Stuyvesant, and Crown Heights — is packing up to leave. A city's material culture is doing a vanishing act. And where is the material going? Back to a version of the world it came from. Many of the cut-rate goods sold in the Lower East Side shops originated in urban sweatshops in China and Pakistan and are eventually passed on as surplus to other poor cities in Africa and Central America. In the wraparound grid of pictures in Analogue we follow recycled clothes from Brooklyn to the city of Kampala in Uganda, where they are sold as new in stores like the Money Is Life House of Garments." Analogue was first exhibited in 2007 at the Wexner Center for the Arts in Columbus, Ohio, and at Documenta XII in Kassel, Germany, followed by presentations at Villa Arson in Nice, and Dia at the Hispanic Society and the Museum of Modern Art in New York and was included in a touring retrospective of Leonard's work which originated in 2007 at the Fotomuseum Winterthur, and later traveled to the Museo Nacional Centro de Arte Reina Sofia, Madrid; MuMOK — Museum Moderner Kunst Stifting Ludwig, Vienna; and Pinakothek der Moderne, Munich. Analogue is in the collection of The Museum of Modern Art, New York, and the Reina Sofia, Madrid. More recent exhibitions have included Serialities at Hauser & Wirth, You See I Am Here After All at Dia: Beacon (2009), Observation Point, Camden Arts Centre, London (2012), an installation at the Chinati Foundation, Marfa, Texas (2013-2014) and the 2014 Whitney Biennial, for which Leonard won the Bucksbaum Award with her work "945 Madison Avenue". In 2018, the Whitney Museum of American Art mounted Leonard's first career retrospective in the United States, an exhibition organized by the Museum of Contemporary Art, Los Angeles, where the show traveled in late 2018.​ Texts by Leonard, an insightful writer, and a pre-eminent thinker on the discipline of photography, have appeared in LTTR, October, and Texte zur Kunst, and in recent monographs on Agnes Martin, James Castle and Josiah McElheny.