The complex biology of respiratory diseases such as asthma is feeding the discovery of various disease phenotypes. Although the clinical management of asthma phenotypes by using a single biomarker (e.g., sputum eosinophils) is successful, emerging evidence shows the requirement of multiscale, high-dimensional biological and clinical measurements to capture the complexity of various asthma phenotypes. High-throughput "omics" technologies, including transcriptomics, proteomics, lipidomics, and metabolomics, are increasingly standardized for biomarker discovery in asthma. The leading principle is obeying available guidelines on omics analysis, thereby strictly limiting false discovery. In this review we address the concept of transcriptomics using microarrays or next-generation RNA sequencing and their applications in asthma, highlighting the strengths and limitations of both techniques, and review metabolomics in exhaled air (breathomics) as a noninvasive alternative for sampling the airways directly. These developments will inevitably lead to the integration of molecular signatures in the phenotyping of asthma and other diseases.