This book is intended to provide an integrated and comprehensive overview of modern approaches to multi-target drug discovery (MTDD) and the state of our knowledge in the over-arching field of polypharmacology. Given the intense current interest in this field, the editors hope that the book will be of significant interest to medicinal and computational chemists in the commercial sector and in academia, as well as the wider drug discovery community. Many readers will already be aware of the serendipitous nature of the discovery of many existing multi-target drugs. In this book the editors focus on the rational and practical execution of MTDD. The chapters are written by widely recognized experts and opinion leaders in the field. The first challenge of MTDD is to identify biologically validated combinations of targets relevant to a disease state. However it is equally important that these disease relevant combinations are chemically tractable from a medicinal chemistry perspective. The book thus follows a natural thread from target identification and validation, through lead generation and lead optimisation, and finally to clinical development. A key feature of the book is a collection of seminal case studies chosen to illustrate the challenges and opportunities of MTDD. These include compounds at various stages of development from pre-clinical to marketed drugs.