Photoacoustic tomography (PAT) is an emerging soft-tissue imaging modality that has great potential for a wide range of biomedical imaging applications.  It can be viewed as a hybrid imaging modality in the sense that it utilizes an optical contrast mechanism combined with ultrasonic detection principles, thereby combining the advantages of optical and ultrasonic imaging while circumventing their primary limitations. The goal of PAT is to reconstruct the distribution of an object's absorbed optical energy density from measurements of pressure wavefields that are induced via the thermoacoustic effect.  In this talk, we review our recent advancements in practical image reconstruction approaches for PAT in heterogeneous acoustic media.  Such advancements include physics-based models of the measurement process and associated inversion methods for reconstructing images from limited data sets.  Applications of PAT to transcranial brain imaging are presented.