Ecogenetics aims at studying the genetics of underlying differential reactions to chemicals in the environment. Genetic modifications due to exposure to foreign substances like toxins due to occupational exposure, dietary constituents, drugs etc. majorly constitute areas studied in the scope of ecogenetics. One of the enzymes that have been at the center-stage of ecogenetic studies is the Paraoxonase 1 (PON1) enzyme. It is one of the oldest enzymes present since the life originated. The presence of an active PON1 enzyme in lower organisms proves that the enzyme’s presence predates human origins. It also had a different native activity and not paraoxonase or arylesterase activities that presumably occurred only later in evolution. The enzyme is also characterized by promiscuity in its specificity towards substrates. These features account for the existence of enzyme isoforms of PON1 and their relevance in xenobiotic metabolism has made PON1 an interesting area of research. Previous studies have assessed PON1 variation in different human populations by evaluating them for activity, genetic variation or PON1 status (constituted by gene variations and activity). The variations have been studied in lieu of their toxicological and pharmacological properties and effects on human health. Sensitivity to chronic exposure of chemicals with the organophosphate moiety like pesticides (chlorpyrifos, malathion, parathion) and nerve gases (soman, sarin) is determined by the PON1 catalytic efficiency and abundance. The ethnic variations in PON1 status and gene frequencies are, hence, keys to understand the differential sensitivity among different groups of populations to chronic exposure of OP compounds. We examined selected populations of India for genetic variations of PON1. Findings show an interesting conglomeration of populations having different PON1 gene frequencies that will be important in assessing OP exposure risk among them. Also, the underlying cause of the systemic variation has not been determined. So, a review of previous research was done to find patterns of genetic variation at key loci of PON1 gene to comprehend the extent of differentiation at these loci. The paper aims at outlining the various aspects of PON1 research with special emphasis on the outcomes of toxicogenetic and pharmacogenetic approaches and the leads they provide for conducting population genetic studies. Deciphering the cause of PON1 variation will improve environment risk assessment exercises that help frame public health initiatives.