An increasing prevalence of asthma noted worldwide has stimulated research on the phenotypic complexity resulting from interaction between the genetic and environmental components. Particularly, an increase in the prevalence of allergic rhinitis and asthma in industrialized countries indicate the importance of pulmonary metabolism of environmental xenobiotics. The arylamine N-acetyltransferases (NATs) are a unique family of enzymes that are involved in the biotransformation and detoxification of hydrazine and arylamine drugs/xenobiotics and could have a major role to play in atopy/asthma pathogenesis. Association studies on NAT1 and NAT2 polymorphisms focused in this review indicate the genetic significance of slow acetylation phenotype in bronchial and occupational asthma as well as in other allergic diseases in different populations worldwide. In contrast, fast acetylators have been found to have higher susceptibility to contact allergic dermatitis. Further in-depth research on the functional role of N- acetylation phenotype in disease pathogenesis is the requisite of the day, so that N-acetylation polymorphisms could serve as a genetic marker. Also, such genetic variations may have important implications in the efficacy of drugs for asthma treatment. The present review also makes a comment on the role of arylalkylamine N-acetyltransferase, an important enzyme involved in the conversion of serotonin to melatonin, in asthma pathogenesis.