Bortolami opened in September 2005. The gallery has presented exhibitions by Richard Aldrich, Barbara Kasten, Ivan Morley, Morgan Fisher, and Tom Burr, artists with whom the gallery has had long-standing relationships. The Bortolami program has expanded to include such artists as Daniel Buren, Ann Veronica Janssens, Caitlin Keogh, Ella Kruglyanskaya, Lena Henke, Renée Green, Lesley Vance, Marina Rheingantz, Deborah Remington, Christine Safa, Paul Mpagi Sepuya, Frieda Toranzo Jaeger, Virginia Overton, and Leda Catunda.
In 2017, Bortolami relocated to the Tribeca neighborhood of Lower Manhattan. The program has also expanded regionally with the launch of the Artist / City initiative, which brings evolving yearlong exhibitions to cities across the United States. These projects include Daniel Buren / Miami, Eric Wesley / St. Louis, Tom Burr / New Haven, Jutta Koether / Philadelphia, Ann Veronica Janssens / Baltimore, Barbara Kasten / Chicago, Paul Pfeiffer / Washington, D.C., and Cecily Brown / Buffalo.