IgE-mediated allergic diseases are among the most prevalent diseases worldwide. The use of extracts in the skin test and the additional use of IgE testing still represent the current basis for the diagnostic work-up. During the past 30 years, knowledge of the molecular structure of allergens has increased dramatically, and the characterization and production of allergenic molecules, as natural purified compounds or recombinant products, is allowing us to approach the allergy diagnostic work-up differently. Much of this is based on the adoption of microtechnology since the first release of a biochip for IgE detection. Its use has prompted the development of new concepts linked to the diagnosis of allergic diseases. This review describes the background of allergy diagnosis and the tools currently used for specific IgE detection. It gives insight into the most recent advancement in the field of biotechnology leading to allergenic molecule availability, microtechnology leading to the routine use of protein biochips for IgE detection, and how they should be combined with information technology.