Arsenic (As), being a metalloid, is well known for its versatile applications to mankind. Arsenic is coined by USEPA as the number one carcinogen. The human body can metabolize arsenic into different forms after intake via water, soils, and food as well as by inhalation. Due to lack of instrumental techniques the total concentration of As was initially considered as the indicator of toxicity. Subsequently, arsenite (AsO33-) was found to be more toxic than arsenate (AsO45-). After the development of hyphenated techniques, the existence of methylated As compounds were reported and methylation was considered the detoxification process in humans. Toxicological studies reported that mono- and dimethylated pentavalent As compounds were less toxic than arsenite (AsIII). During the last decade significant developments in speciation techniques have taken place, which has altered the traditional concept of the toxicity of methylated As compounds. After the identification of trimethylated arsenicals, the methylation of As compounds was considered to be the toxication step in humans. Trivalent dimethylated arsenicals were found to be more toxic than arsine (AsH3). Additional research is on going to elucidate the fate of thioarsenicals regarding toxicity in humans. © 2015 Elsevier Inc. All rights reserved.