Purpose of review The aim of this article is to evaluate the advantages of monitoring the immunological response of non-immediate allergic drug reactions in parallel with the affected tissues, skin and peripheral blood, in order to improve our understanding of the immunological response. Recent findings Several studies have shown that in the skin and peripheral blood, the agents that take part in the development of the immunological reaction express a number of markers that parallel the evolution of the diseases process. These markers include cytokines chemokines and cytotoxic factors as well as many other markers involve din such mechanisms as drug metabolism and signal transition. Summary Monitoring the acute phase response to a drug in the skin with parallel studies in the blood provides clues that increase our understanding of the underlying pathological mechanisms in adverse reactions to drugs with an immunological basis. This approach, together with molecular biology techniques such as microarrays and genomic studies may be useful in future, in better characterizing the clinical subtype and prognosis of nonimmediate allergic drug reactions and generating targeted treatment regimens.