Professor Ortoleva is a leader in the computer modeling of geological and biological processes. He has engaged in groundbreaking research on geochemical systems and has been described as one who "reshaped thinking in geological circles in that it is understood that many repetitive and other patterns observed in the Earth's crust could have arisen spontaneously without the need for an externally-imposed template." He has led this field by promoting the coordination of work among different research centers, and his laboratory attracts researchers from around the world. His work has practical applications in petroleum exploration and production, environmental management and earthquake hazard reduction.
In a second major initiative, Professor Ortoleva and his students are developing a physical chemical model and computer simulator to understand the workings of the living cell. The cell simulator is being used to design well-targeted drugs, optimized treatment strategies, and engineer ideal microbes for the bioremediation of zones of environmental damage.
Ortoleva received the IU Bicentennial Medal in September 2020 in recognition of his distinguished contributions to Indiana University.