Tomosynthesis is a technology that enables the acquisition of three-dimensional (3D) data from a sequence of projection images acquired at different x-ray tube angles. Tomosynthesis imaging is being actively investigated for use in a variety of clinical tasks. Chapter One of this book provides a comparison of reconstruction algorithms in terms of radiation dose reduction of x-ray tomosynthesis. Digital Breast Tomosynthesis (DBT), an emerging and improving breast imaging technology, enhances the diagnosis of early breast cancer by providing in-depth information about the overlapping dense breast tissues with no ambiguities. Chapter Two reviews population-based screening/clinical trials of digital breast tomosynthesis. The last chapter discusses image reconstruction and imaging configuration optimization with a multi-beam parallel digital breast tomosynthesis system.