Transcriptional regulation remains one of the most intriguing and challenging subjects in biomedical research. The catalysis of transcription is a clear example of multiple proteins interacting to orchestrate a biological process, offering a starting point for the study of biological systems. Transcriptional regulation is viewed as one of the principal mechanisms governing the spatial and temporal distribution of gene expression, thus the field of transcriptional regulation provides a natural stage for quantitative studies of multiple gene systems. Building on the body of focused experimental studies and new genomics-driven data, computational biologists are making significant strides in accelerating our understanding of the transcriptional regulatory process in metazoan cells. Recent advances in the computational analysis of the interplay between factors have been fueled by well-defined computational methods for the modeling of the binding of individual transcription factors. We present here an overview of advances in the analysis of regulatory systems and the fundamental methods that underlie the recent developments.