Improved knowledge about the pathogenesis of asthma has facilitated the development of novel drugs and provided hope for patients with severe asthma. After the short- and long-term success of omalizumab in severe allergic phenotype, researchers have targeted patients with severe eosinophilic asthma who comprise up to 45% of adult severe asthma. Interleukin (IL)-5 and IL-5 receptor subunit α play crucial roles in the development, maturation, and operation of eosinophils. Currently, patients treated with anti-IL-5 biologicals depleting eosinophils experience the positive efficacy of these drugs, especially with regard to the reduction of exacerbation rate. The aim of this review was to shed light on severe eosinophilic asthma treatment with these new currently available agents selectively targeting IL-5 or its receptor, discussing their usage including pre-treatment concerns, such as selecting the target population and choosing the right agent among them, and subsequent assessment of relevant effect and safety issues.