This book presents a review concerning the role of mast cells in health and disease. Mast cells were first described by Paul Erlich in his PhD thesis and are considered the remaining cells of an ancient immune system. Indeed, they are placed in common portals of infection, like the urinary and respiratory tracts. The first chapter addresses the role of mast cells in cancer development and progression. Chapters II and III address the role of mast cells in periodontal disease and oral lichen planus, respectively. The role of brain mast cells in neuroinflammation and cognition was described in Chapter IV. Together, these chapters provide the readers an overview of the role of mast cells in different conditions. Since the information presented in this book was obtained from years of works of expertise in the field, we hope that it will be useful for those researchers aiming to better understand the role of mast cells in different conditions.