Fluorosis in man and animals is the resultant of chronic exposure of Fluoride (F) for prolonged period through F contaminated drinking water and foods and industrial F pollution. However, fluoridated water and industrial F emissions are the major sources of F exposure for humans and domestic animals. Chronic F exposure not only deteriorate the health of human beings and animals but also causes diverse adverse toxic effects on hard (teeth and bones) and soft (organs) tissues. Various F induced pathological changes in teeth and bones are known as dental and skeletal fluorosis, respectively. However, skeletal fluorosis is more dangerous and highly significant since it diminishes the mobility at a very early age and develops crippling or lameness bone deformity. Thousands of people and domestic animals are suffering with fluorosis worldwide. Dental fluorosis is rampant and the commonest form of chronic F toxicosis and appears in subjects of almost all age groups. However, children and bovine calves are relatively more sensitive and highly susceptible to F toxicosis and revealed the earliest clinical sign of chronic F poisoning in the form of dental fluorosis. Hence, these are ideal bio-indicators for chronic F intoxication or fluorosis. Nevertheless, the magnitude or severity of fluorosis is much more depending on the density and rate of bio-accumulation of F. Biological samples, milk, urine, blood serum, teeth, nails, etc. are better bio-markers for F intoxication. However, urine F concentration is the best bio-marker for endemic of F and fluorosis. In this communication, ideal bio-indicators and bio-markers for endemic of F and fluorosis and diverse potential determinants influencing the severity of F toxicity (fluorosis) are considered and briefly and critically reviewed. Findings of this review are useful in making and implementation of health policy and the commencement of mitigation and control of fluorosis programme in F endemic areas where it is problematic for human and animal health.