Summary Giant cell arteritis is a primary granulomatous vasculitis characterised by a strict tissue tropism for large and medium-size vessels, occurring in people older than 50 years. Although considerable progress in understanding some of the pathophysiological mechanisms involved in the pathogenesis of giant cell arteritis has been made in the past 10 years, specific triggers of disease and mechanisms of chronic damage have not yet been identified. The definition of a specific pro-inflammatory hierarchy between the multiple cell types and the different cytokines or chemokines involved in the inflammatory process are still unexplored areas of study. The overall goal of precision medicine is to identify the best possible therapeutic approach for an individual or group of individuals with a given disease. The fundamental prerequisite of this approach is the identification, at baseline, of clinical and imaging findings and of molecular biomarkers that allow a precise stratification of patients and an adequate prediction of the therapeutic response. In this regard, the possibility of obtaining temporal artery biopsies for diagnostic purposes offers incredible exploratory possibilities to define different disease pathotypes potentially susceptible to different therapeutic interventions. In this Series paper, we will describe the most recent evidence relating to the pathogenesis of giant cell arteritis, trying to define, if possible, a new pathogenetic-centred approach to patients with giant cell arteritis.