We report the identification of 11 impurities in variously stressed chlorhexidine digluconate (CHG) solutions. The structural assignment of each chlorhexidine digluconate (CHG) impurity involved tentative identification from HPLC-MS data followed by synthesis of the appropriate standard, isolation of the impurity from the chlorhexidine digluconate (CHG) solution by flash chromatography, and comparison of HPLC-MS, HPLC-UV, and NMR data of the impurity with the standard. Six of the synthetic impurity standards represent new compounds. Degradation studies of chlorhexidine digluconate (CHG) solutions systematically stressed by heat, light, and low pH are reported with identification and approximate quantification of resulting impurities. Degradation mechanisms were proposed for each set of stress conditions applied to chlorhexidine digluconate (CHG) solutions. Parallels were noted between the way chlorhexidine digluconate (CHG) degrades in the thermospray interface of the HPLC-MS and the way CHG degrades with shelf time. Similarities were noted in the synthetic starting materials of chlorhexidine digluconate (CHG) and the final degradation products.