CT systems with multi-row detectors or flat-panel imagers provide larger volume coverage in one single gantry rotation and have been widely used for both diagnostic radiology and image-guided therapeutic procedures.  However, the cone-beam nature of the data acquisition with large area detectors poses challenges for image reconstruction. The first challenge is that mathematically exact image reconstruction algorithms have to be developed for each individual cone-beam scan configuration. There is no general analytical algorithm which may be applied to any CT scanning geometry. The second challenge is that new data acquisition geometries must be developed since a single circle/arc scan can not enable artifact free image reconstruction from cone-beam projection data. In this talk, we will present several novel cone-beam image reconstruction frameworks developed in our lab.  These frameworks are used to generate mathematically exact image reconstruction algorithms for each different source trajectory.  As an example we will present images reconstructed from a C-arm based cone-beam CT system.