To date, Girolami's independent research career has encompassed five major themes: mechanistic studies of organometallic reactions such as the polymerization of alkenes and the activation of saturated alkanes, the chemical vapor deposition of thin films from designed molecular precursors, the construction and study of molecular analogs of the photosynthetic reaction center, actinide chemistry, and the synthesis of new molecule-based magnetic materials. His research approach emphasizes the synthesis of new inorganic and organometallic compounds and materials, investigations of their mechanisms of formation, and measurements and interpretations of their physical properties.