Major depressive disorder (MDD) and panic disorder (PD) are common and disabling medical disorders with stress and genetic components. Dysregulation of the stress response of the hypothalamic–pituitary–adrenal axis, including the corticotrophin-releasing hormone (CRH) signaling via primary receptors (CRHR1 and CRHR2), is considered to play a major role for onset and recurrence in MDD and PD. To confirm the association of CRHR1 and CRHR2 with MDD and PD, we investigated 12 single nucleotide polymorphisms (SNPs) (rs4076452, rs7209436, rs110402, rs242924, rs242940, and rs173365 for CRHR1 and rs4722999, rs3779250, rs2267710, rs1076292, rs2284217, and rs226771 for CRHR2) in MDD patients (n = 173), PD patients (n = 180), and healthy controls (n = 285). The SNP rs110402 and rs242924 in the CRHR1 gene and the rs3779250 in the CRHR2 gene were associated with MDD. The SNP rs242924 in the CRHR1 gene was also associated with PD. The T–A–T–G–G haplotype consisting of rs7209436 and rs173365 in CRHR1 was positively associated with MDD. The T–A haplotype consisting of rs7209436 and rs110402 in CRHR1 was positively associated with MDD. The C–C haplotype consisting of rs4722999 and rs3779250 in CRHR2 was associated with PD. These results provide support for an association of CRHR1 and CRHR2 with MDD and PD. © 2012 Wiley Periodicals, Inc.