Understanding disease mechanisms often requires complex and accurate integration of cellular pathways and molecular networks. Systems biology offers the possibility to provide a comprehensive map of the cell's intricate wiring network, which can ultimately lead to decipher the disease phenotype. Here, we describe what biological pathways are, how they function in normal and abnormal cellular systems, limitations faced by databases for integrating data, and highlight how network models are emerging as a powerful integrative framework to understand and interpret the roles of proteins and peptides in diseases.