Reports of natural rubber latex immediate hypersensitivity have increased steadily since the first reported case in 1979. Specific immunoglobulin (Ig)E and IgG4 antibodies to a series of natural rubber latex proteins have been detected in the sera of natural rubber latex-sensitized individuals by many investigators. Different sources of natural rubber latex protein, purification methods coupled with nonstandardized pooled sensitized sera, have contributed to the detection of a wide range of antigens. Antigens in the regions of 14 kd and 30 kd seem the most reproducible. Initial presentation after cutaneous exposure is typically contact urticaria. Aerosolized protein bound to cornstarch powder may lead to rhinitis, conjunctivitis, and bronchospasm. Mucosal and intraoperative parenteral exposure seems to lead to the greatest risk of massive histamine release and anaphylaxis. Although a standardized reagent is not available, the most sensitive diagnostic test remains the prick test. Treatment for the natural rubber latex protein-sensitized individual is natural rubber latex product avoidance. Presurgical histories must emphasize previous difficulty with allergies to balloons, gloves, condoms, etc. Non-natural rubber latex alternatives should be considered routine among risk groups, such as spina bifida and atopic patients with hand eczema, to prevent unnecessary sensitization. This article reviews the natural rubber latex protein source, glove manufacturing variables affecting antigen presence in the finished product, prevalence of natural rubber latex sensitivity, diagnosis, and management.