A particular problem is the safety of administering cephalosporins to penicillin-allergic children, because cephalosporin allergenic determinants have not been properly identified. Cephalosporin antibiotics are widely used to treat common infections and are often the first-line prophylaxis before many types of surgery. So the arm of this study is to determine the frequency of allergic reactions of anaphylactic type to cephalosporins and their cross-reactivity with penicillins. At University Children?s Hospital in Belgrade a group of 1,170 children with suspected anaphylactic allergic reaction to penicillins and/or cephalosporins were tested for the last eight years. Skin tests were performed with standard concentration of penicillins and cephalosporins. In children where skin tests were negative single-blind placebo-controlled challenges were performed. In case of positive skin tests further examinations were interrupted and the children were considered allergic to that drug. The frequency of anaphylactic allergic reactions to cephalosporins is 0.2 % to 17 %, and depends on cephalosporins generation. The cross-reactivity between cephalosporins and penicillins is 0.1 % to 14.5 %, and among cephalosporins is 0 % to 11.7 %.