Spherical indentation with continuous load and depth measurement is a useful technique for characterizing thin film mechanical properties. With this technique, the initial loading is in the elastic range. Therefore the elastic-plastic transition can be observed. However, the calibration of spherical indenters presents special problems. First, the radius of the indenter at the point of contact must be determined, and any deviation from a spherical radius must be evaluated. The shape of the indenter also causes mounting difficulties that can create a relatively large and nonlinear compliance in the testing machine. The calibration of spherical indenters is further complicated, because asperities on the indenter and surface roughness add to the uncertainty in locating the surface of the sample. In addition, spherical indenters are generally made of anisotropic single crystals, and the calculation of their elastic responses must include this anisotropy. To address these issues, a methodology has been developed for the calibration of spherical indenters, whereby indentation experiments are conducted on multiple ceramic materials in the elastic range. The method was used to determine the local radius of synthetic sapphire spherical indenters. The accuracy of this measurement was verified using confocal microscopy. The method was successfully applied to an indenter with a nonlinear machine compliance. Further results involving indentation in the plastic regime are also presented.