Total IgE determination constitutes a good method for the screening of atopic diseases, though its actual value is controversial because normal values of total IgE do not exclude the existence of atopic disease, and high values of total IgE are not pathognomonic of atopy by themselves. The first step in identifying an atopic individual as such, after doing his anamnesis, can be carried out by means of total IgE determination. Most atopic individuals have high IgE values, but a normal result must be carefully interpreted: age and season-related variations must be considered. In general, atopic patients with IgE values greater than 1000 Ul/ml, always have positive specific IgE against some allergen. Antigen-specific IgE will be the next step in the in vitro identification of the responsible allergen. Nowadays, there are more than 400 characterized allergens available for in vitro diagnostic tests and several useful methodologies for specific IgE determination. Specific IgE results obtained with the different methods vary significantly, with absolute agreement in 55-65% of the cases, differences in one IgE class in 20-30% of the cases and differences in more than two classes in 5-10%. The specificity of the anti-IgE antibody used in the assay is of critical importance because any contaminant antibody can render unspecific results. On the other hand, it must be pointed out that there is a compromise between specificity and sensitivity, such that an increase in the sensitivity of a technique leads to a decrease in its specificity. It cannot be said that there is one method which is better than the others; it is better to examine them individually, allergen by allergen. Thus, specific IgE determination varies depending on the type of allergen. In general terms, for inhalant allergens, specificity and sensitivity of the methods are within the range of 85-95%, but these values (especially the specificity) decrease in the case of food allergens, and they are still lower when the allergen is a beta-lactamic drug. There is a good correlation between clinical history and specific IgE against inhalant allergens, and a lower correlation in the case of food allergens. Due to the fact that most food allergens are not standardized, the definitive diagnosis of food hypersensitivity is achieved by means of provocation tests. Nevertheless, negative specific IgE (7-18% of the cases) does not rule out a sensitization against the tested allergen, and a positive specific IgE without symptoms must be carefully interpreted because it can be due to a low degree of sensitization, unable to express clinical symptoms at this moment, but useful in the future as a guide on the disease course. In the evolutive period of the disease, specific IgE levels can be modified in a natural way (in beta-lactam allergy, 50% of the cases with specific IgE become negative after a year), or as an effect of the treatment (e.g., after immunotherapy in the case of Hymenoptera venom allergy), or it can remain positive for a long time, as in the case of pollinosis. On the other hand, the cutoff of the method, and subsequently the range of values to be considered as positive, will depend on the allergen studied. While inhalant allergens (with the exception of some molds) offer relatively high mean values of specific IgE, food and drug allergens yield less significant values. In general, a class greater than 2 is interpreted as clinically significant, class 1 as dubious or negative (depending on the allergen) and class 0 as negative. In the interpretation of the results, the possible presence of IgG and anti-IgE antibodies, capable of modifying the results, will be taken into account. When comparing the diagnostic reliability of specific IgE with respect to other allergologic diagnostic methods, we find a significant and positive correlation of this technique with skin tests (but never greater than 90-95%) and with the histamine release test.