F-actin bundles constitute principal components of a multitude of cytoskeletal processes including stereocilia, filopodia, microvilli, neurosensory bristles, cytoskeletal stress fibers, and the sperm acrosome. The bending, buckling, and stretching behaviors of these processes play key roles in cellular functions ranging from locomotion to mechanotransduction and fertilization. Despite their central importance to cellular function, F-actin bundle mechanics remain poorly understood. Here, we demonstrate that bundle bending stiffness is a state-dependent quantity with three distinct regimes that are mediated by bundle dimensions in addition to crosslink properties. We calculate the complete state-dependence of the bending stiffness and elucidate the mechanical origin of each. A generic set of design parameters delineating the regimes in state-space is derived and used to predict the bending stiffness of a variety of F-actin bundles found in cells. Finally, the broad and direct implications that the isolated state-dependence of F-actin bundle stiffness has on the interpretation of the bending, buckling, and stretching behavior of cytoskeletal bundles is addressed.