Asthma is a complex disease for which genetic predisposition has been widely documented. Considerable evidence supports the hypothesis that polymorphisms in the muscarinic-cholinergic (CHRM) genes could be involved in asthma pathogenesis, bronchial hyperresponsiveness, and mucus secretion. To determine whether single nucleotide polymorphisms (SNPs) or haplotypes in CHRM1, CHRM2, or CHRM3 are associated with asthma in Mexican pediatric population. We performed a case-control study including 398 pediatric cases with asthma and 450 healthy controls. We analyzed 19 SNPs distributed among these three genes. Two of the seven SNPs located in CHRM2, the 3' untranslated region rs8191992 and rs6962027, differed significantly in allele frequencies between patients with asthma and healthy controls [odds ratio (OR) 1.42, 95 % confidence interval (95 % CI) 1.14-1.77, P = 0.001, and OR 1.50, 95 % CI 1.21-1.87, P = 0.0002, respectively]. Statistical significance remained after multiple comparison corrections (P = 0.003 and P = 0.005, respectively). The haplotypes AA and TT, containing both major and minor alleles from rs8191992 and rs6962027, also differed between cases and controls. The haplotype AA occurred at a lower frequency in cases (OR 0.67, 95 % CI 0.53-0.85, P = 0.001) whereas the haplotype TT was overrepresented in cases compared to controls (28 vs 21 %, respectively; OR 1.46, 95 % CI 1.15-1.85, P = 0.002). No association was observed between CHRM1 or CHRM3 SNPs or haplotypes and asthma. CHRM2 polymorphisms are implicated in the genetic etiology of asthma.