All processes occurring in living organisms and responsible for performing vitally necessary functions are carried out by coordinated expression of various groups of genes. A gene regulatory network (GRN) is understood as a set of coordinately expressed genes, their protein products, and the relationships between them. Inferring gene regulatory networks is a fundamental problem in biology that aims to reveal the complex relationships between genes and their regulators. Mathematical methods can be used effectively to solve this and related issues. The existing mathematical approaches are diverse. Among them are thermodynamical models, models using Boolean algebra, graph theory, and models based on the use of dynamical systems. A variety of modeling approaches can be a stimulating prospect for new researchers in this area. The main aim of this Research Topic was to bring together the articles devoted to the contemporary understanding of the application of mathematical methods to the analysis of GRN. Within this topic, six articles have been published that complemented our knowledge of gene networks and their investigations by mathematical methods. Let us look at the articles that were collected in the volume during editorial work.