Abstract: This dissertation discusses novel techniques for interpolation-based software model checking, an approximate method which uses Craig interpolation to compute invariants of programs. Our work addresses two aspects of program analyses based on model checking: verification (the construction of correctness proofs for programs) and falsification (the detection of counterexamples that violate the specification). In Hoare's calculus, a proof of correctness comprises assertions which establish that a program adheres to its specification. The principal challenge is to derive appropriate assertions and loop invariants. Contemporary software verification tools use Craig interpolation (as opposed to traditional predicate transformers such as the weakest precondition) to derive approximate assertions. The performance of the model checker is contingent on the Craig interpolants computed. We present novel interpolation techniques which provide the following advantages over existing methods. Firstly, the resulting interpolants are sound with respect to the bit-level semantics of programs, which is an improvement over interpolation systems that use linear arithmetic over the reals to approximate bit-vector arithmetic and/or do not support bit-level operations. Secondly, our interpolation systems afford us a choice of interpolants and enable us to fine-tune their logical strength and structure. In contrast, existing procedures are limited to a single ad-hoc choice of an interpolant. Interpolation-based verification tools are typically forced to refine an initial approximation repeatedly in order to achieve the accuracy required to establish or refute the correctness of a program. The detection of a counterexample containing a repetitive construct may necessitate one refinement step (involving the computation of additional interpolants) for each iteration of the loop. We present a heuristic that aims to avoid the repeated and computationally expensive construction of interpolants, thus enabling the detection of deeply buried defects such as buffer overflows. Finally, we present an implementation of our techniques and evaluate them on a set of standardised device driver and buffer overflow benchmarks.