Biomechanical factors acting at the level of the lamina cribrosa (LC) are postulated to play a role in retinal ganglion cell dysfunction and loss in glaucoma. In support of this postulate, we now know that a number of cell types (including lamina cribrosa cells) are mechanosensitive. Here we briefly review data indicating cellular stretching, rate of stretching and substrate stiffness may be important mechanosensitivity factors in glaucoma. We then describe how experiments and finite element modeling can be used to quantify the biomechanical environment within the LC, and how this environment depends on IOP. Generic and individual-specific models both suggest that peripapillary scleral properties have a strong influence on LC biomechanics, which can be explained by the observation that scleral deformation drives much of the IOP-dependent straining of the LC. Elegant reconstructions of the LC in monkey eyes have shown that local strains experienced by LC cells depend strongly on laminar beam microarchitecture, which can lead to large local strain elevations. Further modeling, suitably informed by experiments, is needed to better understand lamina cribrosa biomechanics and how they may be involved in glaucomatous optic neuropathy.