Clinical detection of silicosis is currently dependent on radiological abnormalities, a late manifestation of disease. A need for markers of prediction and early detection of pneumoconiosis is imperative for the early evaluation of dust allaying strategies. Understanding of the underlying mechanisms of the etiology of silicosis was instrumental in proposing numerous biomarkers that have been evaluated to assess effects following exposure to crystalline silica dust. Human validation studies have substantiated some of these proposed biomarkers and have argued in favour of their use as biomarkers for crystalline silica-induced pneumoconiosis. A number of 'ideal' biological markers of effect were identified through literature review, viz. TNF, IL-8 and ROS measurement by chemiluminescence (monocyte release), CC16, 8-isoprostanes, total antioxidant levels measured by TEAC, glutathione, glutathione peroxidase, glutathione S-transferase, and PDGF (serum). These identified biomarkers were then evaluated in South African gold miners exposed to silica with and without clinical evidence of silicosis and in control group of men with no silica dust exposure. Results showed that three out of the 10 biomarkers investigated were significantly affected by exposure to silica dust, independently of any effects due to HIV infection, ARV treatment, smoking or age, to an extent that would enable them to be used as biomarkers of early effects due to exposure to crystalline silica. Financial support from Mine Health and Safety Council and permission from Harmony gold mines to recruit volunteer subjects from their mine workforce are gratefully acknowledged.