Abstract Many physicochemical properties of fibrous minerals concur – often simultaneously – in determining the fate of a particle within the human body. A complex chain of physicochemical transformations and biological reactions occur when a mineral fibre comes in contact with biological material and occasionally this results in inhaled material being held in an organism for a very long time. During that time, which might last for decades in the case of highly bio-persistent minerals such as amphibole asbestos, the fibre evolves and reacts with the human body, initially with body fluids and immune system cells, and dynamically interacts with its biological surroundings. To understand the molecular mechanisms of interaction, both bulk and surface properties of toxic – and potentially toxic – mineral fibres have to be considered. Far from being an exhaustive compendium of the enormous numbers of works dealing with the toxicological properties of minerals, this chapter is devoted to the discrimination of the bulk and surface – often interrelated – properties that impart toxic potential to fibrous minerals. To allow the establishment of a common background for a multidisciplinary audience, some general considerations of the factors influencing the health effect of mineral fibres aimed at clarifying some key toxicological concepts, including dose, exposure, clearance and molecular mechanisms, are provided in the initial paragraphs. Because asbestos accounts undoubtedly for the vast bulk of toxicological research on minerals, an essential introduction of the key toxicological properties of non-asbestos mineral fibres is also provided. The chapter is divided into two main sections dealing with bulk and surface properties of mineral fibres variously involved in toxicological response. Specifically, fibre morphology, biopersistence and fibre surface properties, including the generation mechanisms of particle-induced reactive oxygen species (ROS), the investigation of surface active sites and the surface modification induced by the biological environment, are reported and discussed with the support of more than 200 bibliographic references.