The reliability of the biologics used in the treatment of severe asthma is as important as their effectiveness. There are currently six mAbs approved for the treatment of severe asthma (omalizumab, mepolizumab, benralizumab, reslizumab, dupilumab, and tezepelumab). In this review, the safety data obtained from clinical phase studies and real-life studies of these biologics are presented in detail together with our clinical experience. More real-life studies have been done with omalizumab and mepolizumab. It has been shown in these studies that their reliability profiles are quite good. A real-life study with tezepelumab has not been published so far. There are few real-life studies on benralizumab, dupilumab, and reslizumab. However, safety profiles in RCTs with these biologics have been reported similar to placebo. In clinical phase studies, it is seen that the safety profiles of all six biological treatments are quite good.