Cystic fibrosis (CF) is a disease that manifests itself in the context of cell, tissue, and organismal (patho)physiology. While a strong focus on the cystic fibrosis transmembrane conductance regulator (CFTR) since its discovery in 1989 has dominated the field with a wealth of experiments that have provided substantial insight into protein function and structure, a largely untapped area of high relevance to both our basic understanding of CFTR function and its role in clinical disease is the realization that CFTR operates in the context of a cellular network. This is a composite of protein-protein interactions and specific cellular and subcellular environments that balance ion conductance at the cell surface with trafficking through the exocytic and endocytic pathways to promote tissue hydration. To address challenges critical for understanding the system responsible for CFTR physiology and CF pathophysiology, a new era of technologies and methodologies focused on systems-level approaches to analysis of cell and tissue function has emerged. These technologies focus our understanding on the environment supporting protein function (referred to genomics) and the protein composition of the cell (referred to as proteomics) that dictates function. In this section, four chapters focus on emerging "omic" approaches to understanding the cellular environment imposed by message levels in the cell (genomics), the protein composition of the cell and network of interactions dictating cell and CFTR function (proteomics), and the lipid environment (metabolomics) that dictates the functionality of numerous membrane environments in the cell that are integral to CFTR function.