This book is the demonstration of the exciting development in rheumatology for what concerns the knowledge of pathogenesis and the treatment of Rheumatoid Arthritis. The list of authors is a Who is Who's in rheumatology. The book begins with an introductory part on etiology that contains the fundamental chapter on the role that the polygenic nature of rheumatoid arthritis plays in the disease pathogenesis. In this chapter, the problem of HLA association with RA is well presented and the problem of candidate genes analysed for the first time. The chapter on infectious agents is interesting and presents not only viruses but also a part devoted to bacteria (proteus, klebsiella, chlamidia, borrelia, and others) as potential causative agents of the disease. In the section on mechanisms of inflammation, each chapter is thorough and comprehensive and offers a deepening in the understading of the disease pathogenesis. In fact, the whole disease pathogenesis is dissected by the role that each cell (lymphocytes, macrophages, neutrophils, synoviocytes), each mechanism (adhesion and homing, apoptosis) and the cytokine network play. This part is enriched also by a chapter on pain mechansims that explores exhaustively the different aspects of pain generation and the contribution of the peripheral nervous system to the generation of inflammation. Indeed, this section is closed by a chapter that summarises the interaction of all the single factors analysed one-by-one in the previous chapters and gives a general overview on the mechanisms of joint destruction and the consequent therapeutic implications. The section on clinical aspects is comprehensive and enriched by the chapters on imaging and on the utility of molecular markers for the assessment of cartilage damage. However, the feeling of the reader is that, in a further edition of the book , the number of chapters concerning the description of and the approach to the clinical features of the disease should be more numerous. The book might benefit from the evaluation of the problems of the early diagnosis and of the progression of the disease to the late phase, and from a detailed presentation of the differential diagnosis as well as the analysis in detail of the joint and organ involvement. In fact, the limitation of the purely clinical section strongly reduces the attraction of the book for practicioners. The sections on drugs is largely exhaustive and analyses not only glucocorticoids and NSAIDs but all the DMARDs (gold salts, antimalarials, sulfasalazine, methotrexate, and others). This part of the book contains also a useful chapter on intrarticular therapy and a chapter on the new techniques of combining different DMARDs in the treatment of RA. This part is complemented by an excellent section on the surgical treatment of different joints affected by the disease and by practically useful chapters on diet, patient education and psychological and social aspects of rheumatoid arthritis. Probably, the most interesting part for the rheumatologist is the last section of the book that presents for the first time a new and focused way in approaching the management of the disease. All possible compounds that block the effects of proinflammatory cytokines TNF alfa, IL-1, IL-6, IL-8) or that enhance the action of antinflammatory cytokines (IL-4, IL-10, IL-13) are accurately analysed. This section is also enriched by chapters devoted to new treatments targeting the cells (lymphocytes and macrophages) responsible for the disease pathogenesis, to the factors (matrix metalloproteinase) involved in cartilage breakdown, and to the novel inhibitors of transcription factors and their upstream activators that block signal transduction and gene transcription in inflammatory cells. Indeed, the new chapter on clinical trials provides a helpful and enjoyable reading for any physician that needs to understand the modality and the tools with which the efficacy of new therapies in rheumatoid arthritis is tested. This book demonstrates the enormous achievement in the knowledge of pathogenesis that has been transformed in practice in targeted treatments. For this reason it gives to physicians an intellectual and modern pathway of looking at rheumatoid arthritis. The book may be useful for practicing physicians, advanced medical students, and fellows. More likely, the book may be used frequently by specialists in rheumatology to deepen their knowledge into the pathogenesis of the disease as well as it may assist them in the choice of the strategy and in the tailoring of the treatment in rheumatoid arthritis patients.