Some of philosophy's biggest questions, both historically and today, are in-virtue-of questions: In virtue of what is an action right or wrong? In virtue of what am I the same person my mother bore? In virtue of what is an artwork beautiful? Philosophers attempt to answer many of these types of in-virtue-of questions, but philosophers are also increasingly focusing on what an in-virtue-of question is in the first place. Many assume, at least as a working hypothesis, that in-virtue-of questions involve a distinctively metaphysical kind of determinative explanation called "ground." This Handbook surveys the state of the art on ground as well as its connections and applications to other topics. The central issues of ground are discussed in 37 chapters, all written exclusively for this volume by a wide range of leading experts. The chapters are organized into the following sections: I. History II. Explanation and Determination III. Logic and Structure IV. Connections V. Applications Introductions at the start of each section provide an overview of the section's contents, and a list of Related Topics at the end of each chapter points readers to other germane areas throughout the volume. The resulting volume is accessible enough for advanced students and informative enough for researchers. It is essential reading for anyone hoping to get clearer on what the biggest questions of philosophy are really asking.