Registration of single slices from FluoroCT, CineMR, or interventional magnetic resonance imaging to three dimensional (3D) volumes is a special aspect of the two-dimensional (2D)/3D registration problem. Rather than digitally rendered radiographs (DRR), single 2D slice images obtained during interventional procedures are compared to oblique reformatted slices from a high resolution 3D scan. Due to the lack of perspective information and the different imaging geometry, convergence behavior differs significantly from 2D/3D registration applications comparing DRR images with conventional x-ray images. We have implemented a number of merit functions and local and global optimization algorithms for slice-to-volume registration of computed tomography (CT) and FluoroCT images. These methods were tested on phantom images derived from clinical scans for liver biopsies. Our results indicate that good registration accuracy in the range of 0.50 and 1.0 mm is achievable using simple cross correlation and repeated application of local optimization algorithms. Typically, a registration took approximately 1 min on a standard personal computer. Other merit functions such as pattern intensity or normalized mutual information did not perform as well as cross correlation in this initial evaluation. Furthermore, it appears as if the use of global optimization algorithms such as simulated annealing does not improve reliability or accuracy of the registration process. These findings were also confirmed in a preliminary registration study on five clinical scans. These experiments have, however, shown that a strict breath-hold protocol is inevitable when using rigid registration techniques for lesion localization in image-guided biopsy retrieval. Finally, further possible applications of slice-to-volume registration are discussed.