Chlorhexidine is a widely used antiseptic and disinfectant. Compared to its ubiquitous use in medical and non-medical environments, the sensitization rate seems to be low. Multivarious hypersensitivity reactions to the agent have been reported, including delayed hypersensitivity reactions such as contact dermatitis, fixed drug eruptions and photosensitivity reactions. An increasing number of immediate-type allergies such as contact urticaria, occupational asthma and anaphylactic shock have been reported. In the case report, we describe anaphylaxis due to topical skin application of chlorhexidine, confirmed by skin testing and sulfidoleukotriene stimulation test (CAST(R): cellular antigen stimulation test). The potential risk of anaphylactic reactions due to the application of chlorhexidine is well known, especially that application to mucous membranes can cause anaphylactic reactions and was therefore discouraged. The use of chlorhexidine at a 0.05% concentration on wounds and intact skin was so far thought to be safe. Besides our patient, only one other case of severe anaphylactic reaction due to application of chlorhexidine on skin has been reported. Hypersensitivity to chlorhexidine is rare, but its potential to cause anaphylactic shock is probably underestimated. This review should remind all clinicians of an important potential risk of this widely used antiseptic.